PubMed使用手册
网络医学信息检索基本操作步骤
网络文献检索的基本操作步骤昆明医科大学图书馆信息咨询部、文检教研室本手册由2个案例组成，其后配有小贴士，如能按照这些步骤操作，你也一样达到专业水准。
案例1：请查找关于如何治疗高血压的中文文献。
第1步：进入“中国知网”首页（）（当然，也可以进其它的数据库/网站，详见小贴士）。
如图1所示：图1：CNKI首页第2步：进入高级检索页面。
具体做法：点击“学术文献总库”（），结果见图2，点击“高级检索”（），结果见图3。
图2：CNKI标准检索界面图3：CNKI高级检索界面第3步：选择字段。
要选两个字段，一个给（1）高血压，另一个给（2）治疗。
（为什么呢？请看小贴士1）。
具体的做法：点击“全文”右边的箭头（)，选择“主题”，点击“全文”右边的箭头（），选择“主题”，结果见图4。
图4：用“主题”字段检索的界面第4步：分别在第1-2个主题右侧输入“高血压”、“治疗”，出现图5的结果。
图5：CNKI的检索界面第5步：点击，结果出来了（86819篇关于高血压治疗的文献），见图6。
剩下的就是浏览、下载这些结果（在此暂不介绍，有兴趣进一步探讨、学习的同学，可联系QQ：1029860127或者769245112）。
图6：CNKI 数据库关于高血压治疗的文献检索结果界面图7：在google 上查找PubMed 数据库网址的方法案例2：小贴士1：检索策略分析 1.中文医学文献，可以在中文四大数据库中查，它们是（1）中国知网（CNKI ）：有中国硕士、博士论文。
（2）维普数据库（VIP ）：期刊比较全面。
（3）万方数据库（Wanfang ）：目前，收录2007年以来的中华牌杂志的文献。
（4）中国生物医学文献服务系统（SinoMed ）：纯医学，网上个人无法注册。
以上三者均可个人网上注册。
请留意它们各自的特色。
除此之外，NSTL 、百度、谷歌也有不少中文医学文献。
2.以上数据库可在百度或谷歌上查到网址。
3.检索词的分析：我们要查的是“关于高血压治疗方面的文章”，一看就知道有两个检索词：（1）高血压，（2）治疗。
PubMed-中文使用手册
Sort by可以Author, Journal, Publication Date作排序
Send to可選擇Text, File, Clipboard, E-mail,RSS Feed, Order。
以RSS為例，勾選檢索結果的紀錄後，選擇Send to RSS Feed，再按下Create Feed：
prognosis
sห้องสมุดไป่ตู้nsitive/broad
90%/80%
(incidence[MeSH:noexp] OR mortality[MeSH Terms] OR follow up studies[MeSH:noexp] OR prognos*[Text Word] OR predict*[Text Word] OR course*[Text Word])
5.Detail要查驗檢索詞的執行情況，可選擇“Details”鍵。可進行編輯檢索策略或按URL產生網頁加入「我的最愛」。備註：如果用History功能#1 AND #2執行檢索者，無法產生URL。
PubMed Services
Journal Database，查詢該期刊的資訊：全名、簡稱、ISSN。
每篇紀錄之圖示
無摘要/有摘要，如本院有訂購此電子期刊，在IP範圍內可閱讀全文。本院電子期刊清單詳圖書館網頁。
(橘色)PubMed Central,is a free digital archive of full-text journal articles maintained byNIH
(綠色) Free from publisher
specific/narrow
51%/95%
剑桥期刊在线_用户手册
Cambridge Journals Online剑桥期刊在线使用手册孕育于英伦最高学府剑桥大学的剑桥大学出版社成立于1534年，是世界上历史最悠久、规模最大的大学出版社之一。
自从成立以来，剑桥大学出版社一直秉承剑桥大学严谨求实的学术传统，以其卓尔不群的风格和历久弥新的姿态在国际上享有盛誉。
如今，剑桥大学出版社在全球聘用1800多名员工，同时向200多个国家和地区提供图书和期刊，其作者队伍及业务范围遍及全世界。
CUP以专业权威的自然科学和国际领先的人文社科类期刊而闻名于世，2010年共出版236种学术期刊，其中科技类有86种期刊，其中76%被SCI收录；人文社科类有151种期刊，其中66%被SSCI/AHCI收录；医学类有45种期刊，其中65%被SCI收录；工程技术类有39种期刊，有80%被SCI收录。
这些期刊学科跨度广，学术水平高，极力关注各领域的最新研究发展，已成为国内科研和教学的必备资料。
剑桥大学出版社于2007年9月开始为大学用户租用了CERNET的专线，通过专线访问无需支付国际流量费。
2011年剑桥大学出版社计划出版的期刊将达到270种左右，届时剑桥期刊在线的期刊数量及品质将有跨越式的提高。
1.1 期刊浏览每个页面上方都有期刊浏览（Browse Journals）栏目，可以以多种方式浏览期刊：1.1.1 按期刊名称浏览点击“By T itle（按期刊名称浏览）”，进入期刊名称浏览页面。
您可以点击某个英文字母，浏览名称中以该字母为首的期刊。
1.1.2 按学科类别浏览点击“By S ubject（按主题浏览）”，进入主题浏览页面。
您可以选择不同学科主题，浏览相关主题或学科领域的期刊。
1.1.3浏览已订购的期刊点击“Subscribed T o（已订购期刊）”，进入已订购期刊浏览页面。
您可以浏览当前所有有权查阅全文的在线期刊清单，包括贵单位已经订购的、正在试用或可以免费使用的全文在线期刊。
1.1.4浏览免费获取内容点击”Free Content（免费获取）”，进入免费获取内容浏览页面。
循证医学——循证检索
循证医学证据检索尽可能全面！后期人工排除
24
缩小检索范围，提高查准率 1.主题词不扩展，使用下位词，专指主题词 2.主题词/副主题词组配检索 3.限定字段，limits，字段内检索 4.运算符缩小检索范围，AND、WITH、NEAR、 NOT 5.屏幕浏览取词，扩大阅读，可先自由词检索， 再找标准的主题词+副主题词 6.通过“Suggest”功能选词，参考词检索
Narrow,specific search Broad,sensitive search
Clinical prediction guides
Clinical Queries using Research Methodology Filters
pubmed>limits
循证医学信息资源
EMBASE /
注：*数据获取时间为2009-10-10
PubMed中检索循证医学资源
Clinical Queries
Clinical Queries
专门为临床医生研究设计的内置的临床方法学“过滤器” （Clinical Methodology filters）－检索策略模型，由加 拿大流行病学和生物统计学研究人员Haynes Rier公司出品 Excerpta Medica 荷兰《医学文摘》的在线版本 收录自1974年起的内容 涵盖70多个国家/地区出版的4800多种期刊 覆盖各种疾病和药物的信息
Elsevier为同时检索EMBASE和 MEDLINE提供的网络平台
什么是 ?
EMBASE
•1974年起 •4,800 种期刊，其中包括1,800 种 Medline以外的特有期刊
MEDLINE 1966年起 1,800 种Embase以 外的特有期刊 北美文献为主
PubMed使用手册
PubMed使用手册【基本查询方法】∙一个检索词：一个单词：在文本框中输入检索词，按GO查询。
含两个单词以上的检索词：需要加双引号，注意是英文输入状态下的双引号。
如："ultrasonic diagnosis"是正确的，“ultrasonic diagnosis”是错误的∙两个以上的检索词：可使用 AND、OR 连接各检索词。
如："three dimensional ultrasound" AND thyroid ∙可以在“limit”菜单下限制文献出版的时间、语种等等。
【完全手册】PubMed 系统的主要特点1.词汇自动转换功能（Automatic Term Mapping）在PubMed主页的检索提问框中键入检索词，系统将按顺序使用如下4种表或索引，对检索词进行转换后再检索。
（1）MeSH转换表（MeSH Translation Table），包括MeSH词、参见词、副主题词等。
如果系统在该表中发现了与检索词相匹配的词，就会自动将其转换为相应的MeSH词和TextWord词（题名词和文摘词）进行检索。
例如：键入"Vitamin h"，系统将其转换成"Biotin [MeSH Tems] OR Vitamin h [Textword]"后进行检索。
（2）刊名转换表（Journal Tanslation Table），包括刊名全称、MEDLINE 形式的缩写和ISSN号。
该转换表能把键入的刊名全称转换为"MEDLINE缩写[Journal Name]"后进行检索。
如：在检索提问框中键入："new england journal of medicine", PubMed将其转换为"N Engl J Med [Journal Name]"后进行检索。
（3）短语表（Phrase list）。
PubMed医学文献检索系统.
PubMed医学文献检索系统PubMed是因特网上重要的免费文献检索系统。
目前全球最著名的医学文献数据库系统是美国国立医学图书馆的MEDLINE，该数据库重数据免费提供给各个检索系统的开发商，因此在因特网上有重多的免费MEDLINE检索系统。
这些系统所涵盖的文献年代、检索结果的输出格式以及检索途径各不相同，但是，目前被医务人员广泛使用的仍然是美国国立医学图书馆的PubMed系统PubMed和NCBI：1．美国国立医学图书馆“NLM”2．早在1879年，编译医学文献的检索刊物IM3．1964年采用计算机进行电子编辑和排版，在此基础上开发了“医学文献分析与检索系统”（即著名的MEDLARS）4．1971年正式建立了钙系统的联机系统，称为“MEDLARS联机检索系统，MEDLARS online,既MEDLINE 系统。
5．PubMed则是NLM的国家生物信息中心（National Center for Biotechnology Information, NCBI）开发的一个以网络为基础的检索系统，自1997年免费提供服务PubMed ――特点：PubMed具有MEDLINE 所具有的各种检索和数据库优势，同时还具有以下特点：⏹连接广泛：包括对外链接和对内链接，对内指与NCBI其它数据库的链接和PubMed文献相似度计算后的相关文献链接，对外连接指出版商提供的文献全文的连接，有免费和需要注册的。
⏹更新速度快：出版商直接把电子版提供给NLM⏹收录文献范围广：三个层次的数据库：MEDLINE数据库、PreMEDLINE数据库和出版商直接提供的文献数据库等PubMed ――收录范围总体包括：⏹收录年限：1966～⏹收录内容：70多个国家和地区的4000余种生物医学期刊的文献和一些非医学内容的文献，主要是MEDLINE。
内容涉及医学、护理、牙科、兽医、健康保健系统、前临床医学等学科，另外有非医学内容的文献，如science 和nature中具有地理学方面的文献。
新版Pubmed最全实用教程（超全收藏版）
新版Pubmed最全实用教程（超全收藏版）PubMed 是一个免费的搜寻引擎，提供生物医学方面的论文搜寻以及摘要。
它的数据库来源为MEDLINE。
其核心主题为医学，但亦包括其他与医学相关的领域，像是护理学或者其他健康学科。
它同时也提供对于相关生物医学资讯上相当全面的支援，像是生化学与细胞生物学。
该搜寻引擎是由美国国立医学图书馆提供，作为 Entrez 资讯检索系统的一部分。
PubMed 的资讯并不包括期刊论文的全文，但可能提供指向全文提供者(付费或免费)的链接。
PubMed是因特网上使用最广泛的免费MEDLINE,是美国国家医学图书馆(NLM)所属的国家生物技术信息中心(NCBI)于2000年4月开发的,基于WEB的生物医学信息检索系统,它是NCBI Entrez整个数据库查询系统中的一个。
PubMed界面提供与综合分子生物学数据库的链接，其内容包括:DNA与蛋白质序列，基因图数据，3D蛋白构象，人类孟德尔遗传在线，也包含着与提供期刊全文的出版商网址的链接等。
PubMed系统的特征工具栏提供辅助检索功能、侧栏提供其它检索如期刊数据库检索、主题词数据库检索和特征文献检索。
提供原文获取服务免费提供题录和文摘，可与提供原文的网址链接，提供检索词自动转换匹配，操作简便、快捷。
Pubmed最近也是改头换面了，为了能够帮助大家快速熟悉上手新版Pubmed，我们这里进行了常用功能的总结，供大家参考。
首页是这样的：目录•基本检索•高级检索•Mesh主题词检索•常用检索技巧•如何让Pubmed自动发送最新文献•如何使用Pubmed直接复制黏贴参考文献基本检索基本检索是PubMed最常用的检索方式。
在PubMed基本检索框中输入检索词，点击Search即可检索文献。
比如在检索框中直接输入septic shock，点击检索。
结果显示界面如下，中间主体内容为检索获得的文献，左侧主体内容为Pubmed自带或者你自己自主设置的过滤器。
美国国家生物信息中心使用介绍
NCBI (National Center for Biotechnology Information), 美国国家生物技术信息中心[url]/[/url]NCBI是NIH的国立医学图书馆（NLM）的一个分支。
NCBI提供检索的服务包括：1．GenBank（NIH遗传序列数据库）：一个可以公开获得所有的DNA序列的注释过的收集。
GenBank是由NCBI受过分子生物学高级训练的工作人员通过来自各个实验室递交的序列和同国际核酸序列数据库（EMBL和DDBJ）交换数据建立起数据库的。
它同日本和欧洲分子生物学实验室的DNA数据库共同构成了国际核酸序列数据库合作。
这三个组织每天交换数据。
其中的数据以指数形式增长，最近的数据为它已经有来自47000个物种的30亿个碱基。
2．Molecular Databases（分子数据库）：Nucleotide Sequence（核酸序列库）：从NCBI其他如Genbank数据库中收集整理核酸序列，提供直接的检索。
Protein Sequence （蛋白质序列库）：与核酸类似，也是从NCBI多个不同资源中编译整理的，方便研究者的直接查询。
Structure（结构）-——关于NCBI结构小组的一般信息和他们的研究计划，另外也可以访问三维蛋白质结构的分子模型数据库（MMDB）和用来搜索和显示结构的相关工具。
MMDB：分子模型数据库—一个关于三维生物分子结构的数据库，结构来自于X-ray晶体衍射和NMR色谱分析。
Taxonomy（分类学）——NCBI的分类数据库，包括大于7万余个物种的名字和种系，这些物种都至少在遗传数据库中有一条核酸或蛋白序列。
其目的是为序列数据库建立一个一致的种系发生分类学。
3．Literature Databases（文献数据库）（1）PubMed是NLM提供的一项服务，能够对MEDLINE上超过1200万条的上世纪六十年代中期至今的杂志引用和其他的生命科学期刊进行访问，并可以连接到参与的出版商网络站点的全文文章和其他相关资源。
pubmed使用手册1
The NCBI Handbookdata daily so that all three databases should contain the same set of sequences. Members of the DDBJ, EMBL, and GenBank staff meet annually to discuss technical issues, and an international advisory board meets with the database staff to provide additional guidance. An entry can only be updated by the database that initially prepared it to avoid conflicting data at the three sites.The Collaboration created a Feature Table Definition that outlines legal features and syntax for the DDBJ, EMBL, and GenBank feature tables. The purpose of this document is to standardize annotation across the databases. The presentation and format of the data are different in the three databases, however, the underlying biological information is the same.Confidentiality of Data When scientists submit data to GenBank, they have the opportunity to keep their data confidential for a specified period of time. This helps to allay concerns that the availability of their data in GenBank before publication may compromise their work. When the article containing the citation of the sequence or its Accession number is published, the sequence record is released. The database staff request that submitters notify GenBank of the date of publication so that the sequence can be released without delay. The request to release should be sent to gb-admin@.Direct Submissions The typical GenBank submission consists of a single, contiguous stretch of DNA or RNA sequence with annotations. The annotations are meant to provide an adequate representation of the biological information in the record. The GenBank Feature Table Definition describes the various features and subsequent qualifiers agreed upon by the International Nucleotide Sequence Database Collaboration.Currently, only nucleotide sequences are accepted for direct submission to GenBank. These include mRNA sequences with coding regions, fragments of genomic DNA with a single gene or multiple genes, and ribosomal RNA gene clusters. If part of the nucleotide sequence encodes a protein, a conceptual translation, called a CDS (coding sequence), is annotated. The span of the CDS feature is mapped to the nucleotide sequence encoding the protein. A protein Accession number (/protein_id) is assigned to the translation product, which will subsequently be added to the protein databases.Multiple sequences can be submitted together. Such batch submissions of non-relatedsequences may be processed together but will be displayed in Entrez (Chapter 15) as single records. Alternatively, by using the Sequin submission tool (Chapter 12), a submitter can specify that several sequences are biologically related. Such sequences are classified as environmental sample sets, population sets, phylogenetic sets, mutation sets, or segmented sets. Each sequence within a set is assigned its own Accession number and can be viewed independently in Entrez. However, with the exception of segmented sets, each set is also indexed within the PopSet division of Entrez, thus allowing scientists to view the relationship between the sequences.What defines a set? Environmental sample, population, phylogenetic, and mutation sets all contain a group of sequences that spans the same gene or region of the genome. Environmental samples are derived from a group of unclassified or unknown organisms. A population set contains sequences from different isolates of the same organism. A phylogenetic set contains sequences from different organisms that are used to determine the phylogenetic relationship between them. Sequencing multiple mutations within a single gene gives rise to a mutation set.The NCBI HandbookThe NCBI HandbookThe NCBI HandbookThe NCBI HandbookAll sets, except segmented sets, may contain an alignment of the sequences within them and might include external sequences already present in the database. In fact, the submitter can begin with an existing alignment to create a submission to the database using the Sequin submission tool. Currently, Sequin accepts FASTA+GAP, PHYLIP, MACAW, NEXUS Interleaved, and NEXUS Contiguous alignments. Submitted alignments will be displayed in the PopSet section of Entrez.Segmented sets are a collection of noncontiguous sequences that cover a specified genetic region. The most common example is a set of genomic sequences containing exons from a single gene where part or all of the intervening regions have not been sequenced. Each member record within the set contains the appropriate annotation, exon features in this case. However,the mRNA and CDS will be annotated as joined features across the individual records.Segmented sets themselves can be part of an environmental sample, population, phylogenetic,or mutation set.Bulk Submissions: High-Throughput Genomic Sequence (HTGS)HTGS entries are submitted in bulk by genome centers, processed by an automated system,and then released to GenBank. Currently, about 30 genome centers are submitting data for a number of organisms, including human, mouse, rat, rice, and Plasmodium falciparum , the malaria parasite.HTGS data are submitted in four phases of completion: 0, 1, 2, and 3. Phase 0 sequences are one-to-few reads of a single clone and are not usually assembled into contigs. They are low-quality sequences that are often used to check whether another center is already sequencing a particular clone. Phase 1 entries are assembled into contigs that are separated by sequence gaps,the relative order and orientation of which are not known (Figure 1). Phase 2 entries are also unfinished sequences that may or may not contain sequence gaps. If there are gaps, then the contigs are in the correct order and orientation. Phase 3 sequences are of finished quality and have no gaps. For each organism, the group overseeing the sequencing effort determines the definition of finished quality.The NCBI HandbookThe NCBI HandbookThe NCBI HandbookThe NCBI HandbookDiagram showing the orientation and gaps that might be expected in high-throughput sequence from phases 1, 2, and 3.Phase 0, 1, and 2 records are in the HTG division of GenBank, whereas phase 3 entries go into the taxonomic division of the organism, for example, PRI (primate) for human. An entry keeps its Accession number as it progresses from one phase to another but receives a new Accession.Version number and a new gi number each time there is a sequence change.Submitting Data to the HTG DivisionTo submit sequences in bulk to the HTG processing system, a center or group must set up an FTP account by writing to htgs-admin@. Submitters frequently use two tools to create HTG submissions, Sequin or fa2htgs. Both of these tools require FASTA-formatted sequence, i.e., a definition line beginning with a “greater than” sign (“>”) followed by a unique identifier for the sequence. The raw sequence appears on the lines after the definition line. For sequences composed of contigs separated by gaps, a modified FASTA format is used. In addition, Sequin users must modify the Sequin configuration file so that the HTG genome center features are enabled.fa2htgs is a command-line program that is downloaded to the user's computer. The submitter invokes a script with a series of parameters (arguments) to create a submission. It has an advantage over Sequin in that it can be set up by the user to create submissions in bulk from multiple files.Submissions to HTG must contain three identifiers that are used to track each HTG record: the genome center tag, the sequence name, and the Accession number. The genome center tag is assigned by NCBI and is generally the FTP account login name. The sequence name is a unique identifier that is assigned by the submitter to a particular clone or entry and must be unique within the group's submissions. When a sequence is first submitted, it has only a sequence name and genome center tag; the Accession number is assigned during processing. All updates to that entry must include the center tag, sequence name, and Accession number, or processing will fail.The HTG Processing PathwaySubmitters deposit HTGS sequences in the form of Seq-submit files generated by Sequin,fa2htgs, or their own ASN.1 dumper tool into the SEQSUBMIT directory of their FTP account.Every morning, scripts automatically pick up the files from the FTP site and copy them to the processing pathway, as well as to an archive. Once processing is complete and if there are no errors in the submission, the files are automatically loaded into GenBank. The processing time is related to the number of submissions that day; therefore, processing can take from one to many hours.Entries can fail HTG processing because of three types of problems:1Formatting: submissions are not in the proper Seq-submit format.The NCBI HandbookThe NCBI Handbook The NCBI Handbook The NCBI Handbook2Identification: submissions may be missing the genome center tag, sequence name,or Accession number, or this information is incorrect.3Data: submissions have problems with the data and therefore fail the validator checks.When submissions fail HTG processing, a GenBank annotator sends email to the sequencing center, describing the problem and asking the center to submit a corrected entry. Annotators do not fix incorrect submissions; this ensures that the staff of the submitting genome center fixes the problems in their database as well.The processing pathway also generates reports. For successful submissions, two files are generated: one contains the submission in GenBank flat file format (without the sequence);and another is a status report file. The status report file, ac4htgs, contains the genome center,sequence name, Accession number, phase, create date, and update date for the submission.Submissions that fail processing receive an error file with a short description of the error(s)that prevented processing. The GenBank annotator also sends email to the submitter, explaining the errors in further detail.Additional Quality Assurance When successful submissions are loaded into GenBank, they undergo additional validation checks. If GenBank annotators find errors, they write to the submitters, asking them to fix these errors and submit an update.Whole Genome Shotgun Sequences (WGS)Genome centers are taking multiple approaches to sequencing complete genomes from a number of organisms. In addition to the traditional clone-based sequencing whose data are being submitted to HTGS, these centers are also using a WGS approach to sequence the genome. The shotgun sequencing reads are assembled into contigs, which are now being accepted for inclusion in GenBank. WGS contig assemblies may be updated as the sequencing project progresses and new assemblies are computed. WGS sequence records may also contain annotation, similar to other GenBank records.Each sequencing project is assigned a stable project ID, which is made up of four letters. The Accession number for a WGS sequence contains the project ID, a two-digit version number,and six digits for the contig ID. For instance, a project would be assigned an Accession number AAAX00000000. The first assembly version would be AAAX01000000. The last six digits of this ID identify individual contigs. A master record for each assembly is created. This master record contains information that is common among all records of the sequencing project, suchas the biological source, submitter, and publication information. There is also a link to the range of Accession numbers for the individual contigs in this assembly.WGS submissions can be created using tbl12asn, a utility that is packaged with the Sequin submission software. Information on submitting these sequences can be found at Whole Genome Shotgun Submissions.Bulk Submissions: EST, STS, and GSSExpressed Sequence Tags (EST), Sequence Tagged Sites (STSs), and Genome SurveySequences (GSSs) sequences are generally submitted in a batch and are usually part of a large sequencing project devoted to a particular genome. These entries have a streamlined submission process and undergo minimal processing before being loaded to GenBank.ESTs are generally short (<1 kb), single-pass cDNA sequences from a particular tissue and/or developmental stage. However, they can also be longer sequences that are obtained byThe NCBI HandbookThe NCBI HandbookThe NCBI HandbookThe NCBI Handbookdifferential display or Rapid Amplification of cDNA Ends (RACE) experiments. The common feature of all ESTs is that little is known about them; therefore, they lack feature annotation.STSs are short genomic landmark sequences (1). They are operationally unique in that they are specifically amplified from the genome by PCR amplification. In addition, they define a specific location on the genome and are, therefore, useful for mapping.GSSs are also short sequences but are derived from genomic DNA, about which little is known.They include, but are not limited to, single-pass GSSs, BAC ends, exon-trapped genomic sequences, and Alu PCR sequences.EST, STS, and GSS sequences reside in their respective divisions within GenBank, rather than in the taxonomic division of the organism. The sequences are maintained within GenBank in the dbEST, dbSTS, and dbGSS databases.Submitting Data to dbEST, dbSTS, or dbGSS Because of the large numbers of sequences that are submitted at once, dbEST, dbSTS, and dbGSS entries are stored in relational databases where information that is common to all sequences can be shared. Submissions consist of several files containing the common information, plus a file of the sequences themselves. The three types of submissions have different requirements, but all include a Publication file and a Contact file. See the dbEST,dbSTS, and dbGSS pages for the specific requirements for each type of submission.In general, users generate the appropriate files for the submission type and then email the files to batch-sub@. If the files are too big for email, they can be deposited into a FTP account. Upon receipt, the files are examined by a GenBank annotator, who fixes any errors when possible or contacts the submitter to request corrected files. Once the files are satisfactory, they are loaded into the appropriate database and assigned Accession numbers.Additional formatting errors may be detected at this step by the data-loading software, such as double quotes anywhere in the file or invalid characters in the sequences. Again, if the annotator cannot fix the errors, a request for a corrected submission is sent to the user. After all problems are resolved, the entries are loaded into GenBank.Bulk Submissions: HTC and FLIC HTC records are High-Throughput cDNA/mRNA submissions that are similar to ESTs but often contain more information. For example, HTC entries often have a systematic gene name (not necessarily an official gene name) that is related to the lab or center that submitted them,and the longest open reading frame is often annotated as a coding region.FLIC records, Full-Length Insert cDNA, contain the entire sequence of a cloned cDNA/mRNA.Therefore, FLICs are generally longer, and sometimes even full-length, mRNAs. They are usually annotated with genes and coding regions, although these may be lab systematic names rather than functional names.HTC SubmissionsHTC entries are usually generated with Sequin or tbl2asn, and the files are emailed to gb-sub@. If the files are too big for email, then by prior arrangement, thesubmitter can deposit the files by FTP and send a notification to gb-admin@ that files are on the FTP site.The NCBI HandbookThe NCBI HandbookThe NCBI HandbookThe NCBI HandbookHTC entries undergo the same validation and processing as non-bulk submissions. Once processing is complete, the records are loaded into GenBank and are available in Entrez and other retrieval systems.FLIC Submissions FLICs are processed via an automated FLIC processing system that is based on the HTG automated processing system. Submitters use the program tbl2asn to generate their submissions. As with HTG submissions, submissions to the automated FLIC processing system must contain three identifiers: the genome center tag, the sequence name (SeqId), and the Accession number. The genome center tag is assigned by NCBI and is generally the FTP account login name. The sequence name is a unique identifier that is assigned by the submitter to a particular clone or entry and must be unique within the group's FLIC submissions. When a sequence is first submitted, it has only a sequence name and genome center tag; the Accession number is assigned during processing. All updates to that entry include the center tag, sequence name, and Accession number, or processing will fail.The FLIC Processing Pathway The FLIC processing system is analogous to the HTG processing system. Submitters deposit their submissions in the FLICSEQSUBMIT directory of their FTP account and notify us that the submissions are there. We then run the scripts to pick up the files from the FTP site and copy them to the processing pathway, as well as to an archive. Once processing is complete and if there are no errors in the submission, the files are automatically loaded into GenBank.As with HTG submissions, FLIC entries can fail for three reasons: problems with the format,problems with the identification of the record (the genome center, the SeqId, or the Accession number), or problems with the data itself. When submissions fail FLIC processing, a GenBank annotator sends email to the sequencing center, describing the problem and asking the center to submit a corrected entry. Annotators do not fix incorrect submissions; this ensures that the staff of the submitting genome center fixes the problems in their database as well. At the completion of processing, reports are generated and deposited in the submitter's FTP account,as described for HTG submissions.Submission Tools Direct submissions to GenBank are prepared using one of two submission tools, BankIt or Sequin.BankItBankIt is a Web-based form that is a convenient and easy way to submit a small number of sequences with minimal annotation to GenBank. To complete the form, a user is prompted to enter submitter information, the nucleotide sequence, biological source information, and features and annotation pertinent to the submission. BankIt has extensive Help documentation to guide the submitter. Included with the Help document is a set of annotation examples that detail the types of information that are required for each type of submission. After theinformation is entered into the form, BankIt transforms this information into a GenBank flatfile for review. In addition, a number of quality assurance and validation checks ensure that the sequence submitted to GenBank is of the highest quality. The submitter is asked to include spans (sequence coordinates) for the coding regions and other features and to include amino acid sequence for the proteins that derive from these coding regions. The BankIt validator compares the amino acid sequence provided by the submitter with the conceptual translation of the coding region based on the provided spans. If there is a discrepancy, the submitter is requested to fix the problem, and the process is halted until the error is resolved. To preventThe NCBI HandbookThe NCBI HandbookThe NCBI HandbookThe NCBI Handbookthe deposit of sequences that contain cloning vector sequence, a BLAST similarity search is performed on the sequence, comparing it to the VecScreen database. If there is a match to this database, the user is asked to remove the contaminating vector sequence from their submission or provide an explanation as to why the screen was positive. Completed forms are saved in ASN.1 format, and the entry is submitted to the GenBank processing queue. The submitter receives confirmation by email, indicating that the submission process was successful.Sequin Sequin is more appropriate for complicated submissions containing a significant amount of annotation or many sequences. It is a stand-alone application available on NCBI's FTP site.Sequin creates submissions from nucleotide and amino acid sequences in FASTA format with tagged biological source information in the FASTA definition line. As in BankIt, Sequin has the ability to predict the spans of coding regions. Alternatively, a submitter can specify the spans of their coding regions in a five-column, tab-delimited table and import that table into Sequin. For submitting multiple, related sequences, e.g., those in a phylogenetic or population study, Sequin accepts the output of many popular multiple sequence-alignment packages,including FASTA+GAP, PHYLIP, MACAW, NEXUS Interleaved, and NEXUS Contiguous.It also allows users to annotate features in a single record or a set of records globally. For more information on Sequin, see Chapter pleted Sequin submissions should be emailed to GenBank at gb-sub@rger files may be submitted by SequinMacrosend.Sequence Data Flow and Processing: From Laboratory to GenBank Triage All direct submissions to GenBank, created either by Sequin or BankIt, are processed by the GenBank annotation staff. The first step in processing submissions is called triage. Within 48hours of receipt, the database staff reviews the submission to determine whether it meets the minimal criteria for incorporation into GenBank and then assigns an Accession number to each sequence. All sequences must be >50 bp in length and be sequenced by, or on behalf of, the group submitting the sequence. GenBank will not accept sequences constructed in silico ;noncontiguous sequences containing internal, unsequenced spacers; or sequences for which there is not a physical counterpart, such as those derived from a mix of genomic DNA and mRNA. Submissions are also checked to determine whether they are new sequences or updates to sequences submitted previously. After receiving Accession numbers, the sequences are put into a queue for more extensive processing and review by the annotation staff.IndexingTriaged submissions are subjected to a thorough examination, referred to as the indexing phase.Here, entries are checked for:1Biological validity. For example, does the conceptual translation of a coding regionmatch the amino acid sequence provided by the submitter? Annotators also ensure that the source organism name and lineage are present, and that they are represented in NCBI's taxonomy database. If either of these is not true, the submitter is asked to correct the problem. Entries are also subjected to a series of BLAST similaritysearches to compare the annotation with existing sequences in GenBank.2Vector contamination. Entries are screened against NCBI's UniVec database to detect contaminating cloning vector.The NCBI HandbookThe NCBI HandbookThe NCBI HandbookThe NCBI Handbook3Publication status. If there is a published citation, PubMed and MEDLINE identifiers are added to the entry so that the sequence and publication records can be linked in Entrez.4Formatting and spelling. If there are problems with the sequence or annotation, the annotator works with the submitter to correct pleted entries are sent to the submitter for a final review before release into the public database. If the submitters requested that their sequences be released after processing, they have 5 days to make changes prior to release. The submitter may also request that GenBank hold their sequence until a future date. The sequence must become publicly available once the Accession number or the sequence has been published. The GenBank annotation staff currently processes about 1,900 submissions per month, corresponding to approximately 20,000sequences.GenBank annotation staff must also respond to email inquiries that arrive at the rate of approximately 200 per day. These exchanges address a range of topics including:•updates to existing GenBank records, such as new annotation or sequence changes •problem resolution during the indexing phase •requests for release of the submitter's sequence data or an extension of the hold date •requests for release of sequences that have been published but are not yet available in GenBank •lists of Accession numbers that are due to appear in upcoming issues of a publisher's journals •reports of potential annotation problems with entries in the public database •requests for information on how to submit data to GenBank One annotator is responsible for handling all email received in a 24-hour period, and all messages must be acted upon and replied to in a timely fashion. Replies to previous emails are forwarded to the appropriate annotator.Processing Tools The annotation staff uses a variety of tools to process and update sequence submissions.Sequence records are edited with Sequin, which allows staff to annotate large sets of records by global editing rather than changing each record individually. This is truly a time saver because more than 100 entries can be edited in a single step (see Chapter 12 on Sequin formore details). Records are stored in a database that is accessed through a queue management tool that automates some of the processing steps, such as looking up taxonomy and PubMed data, starting BLAST jobs, and running automatic validation checks. Hence, when an annotator is ready to start working on an entry, all of this information is ready to view. In addition, all of the correspondence between GenBank staff and the submitter is stored with the entry. For updates to entries already present in the public database, the live version of the entry is retrieved from ID, and after making changes, the annotator loads the entry back into the public database.This entry is available to the public immediately after loading.Microbial GenomesThe GenBank direct submissions group has processed more than 50 complete microbialgenomes since 1996. These genomes are relatively small in size compared with their eukaryotic counterparts, ranging from five hundred thousand to five million bases. Nonetheless, these genomes can contain thousands of genes, coding regions, and structural RNAs; therefore,processing and presenting them correctly is a challenge. Currently, the DDBJ/EMBL/GenBankThe NCBI HandbookThe NCBI HandbookThe NCBI HandbookThe NCBI HandbookNucleotide Sequence Database Collaboration has a 350-kilobase (kb) upper size limit for sequence entries. Because a complete bacterial genome is larger than this arbitrary limit, it must be split into pieces. GenBank routinely splits complete microbial genomes into 10-kb pieces with a 60-bp overlap between pieces. Each piece contains approximately 10 genes. A CON entry, containing instructions on how to put the pieces back together, is also made. The CON entry contains descriptor information, such as source organism and references, as well as a join statement providing explicit instructions on how to generate the complete genome from the pieces. The Accession number assigned to the CON record is also added as a secondary Accession number on each of the pieces that make up the complete genome (see Figure 2).Page 10The NCBI Handbook The NCBI Handbook The NCBI Handbook The NCBI HandbookA GenBank CON entry for a complete bacterial genome The information toward the bottom of the record describes how to generate the complete genome from the pieces.Submitting and Processing Data Submitters of complete genomes are encouraged to contact us at genomes@before preparing their entries. A FTP account is required to submit large files, and the submission should be deposited at least 1 month before publication to allow for processing time and coordinated release before publication. In addition, submitters are required to follow certain guidelines, such as providing unique identifiers for proteins and systematic names for all genes. Entries should be prepared with the submission tool tbl2asn, a utility that is part of the Sequin package (Chapter 12). This utility creates an ASN.1 submission file from a five-column, tab-delimited file containing feature annotation, a FASTA-formatted nucleotide sequence, and an optional FASTA-formatted protein sequence.Complete genome submissions are reviewed by a member of the GenBank annotation staff to ensure that the annotation and gene and protein identifiers are correct, and that the entry is in proper GenBank format. Any problems with the entry are resolved through communication with the submitter. Once the record is complete, the genome is carefully split into its component pieces. The genome is split so that none of the breaks occurs within a gene or coding region.A member of the annotation staff performs quality assurance checks on the set of genomeThe NCBI HandbookThe NCBI HandbookThe NCBI HandbookThe NCBI Handbook。
如何进行质粒查找
经常在坛子里看到一些人求助质粒图谱，很多时候我发现其实有些质粒图谱还是很容易找到了，刚开始帮忙查找了下，还公布了一些查找质粒图谱比较好的网站，后来看得多了，很多时候，这样的帖子直接跳过了。
今天又看到几个求质粒图谱的帖子，因此决定就查找质粒图谱的方法，写个总结帖子，希望对虫子们有些帮助。
这些方法，大部分是自己学习的过程中积累的，也许总结得还不够全面，望其他虫友指正。
方法一：安装软件Vector NT做分子实验，经常和不同的质粒打交道，了解各种质粒的图谱信息是必需的，invitrogen 公司的这款软件绝对是分子生物学虫子们的福音，功能强大、界面美观，使用起来很人性化。
后面的很多方法都是基于在这款软件的使用之上，因此个人觉得要想对质粒图谱了解更直观，安装这款软件是非常必要的。
而且，一旦安装了这款软件，你就发现这款软件的软件包里面会包括invitrogen公司的所有质粒图谱信息和其他比较常见和经典的质粒图谱（不是有虫子求pRS系列质粒吗？帖子链接/bbs/viewthread.php?tid=3103223&fpage=1，如下图，数据库中本身就有很多）。
这里就不一一细说，各位虫子可以自己体验下。
（这款软件的下载和使用说明书站内很多）方法二：查找质粒图谱的网站：这个之前有人求助质粒图谱时，我在回应求助帖里面公布过几个我经常用的网址，估计不是专题，很多人没看到，现在在此重新总结下1.Vector Database地址：https:///g?a=vdb这个网站很页面很人性化，直入主题，也是我经常用到一个网站，比如同样这个帖子求pRS 类质粒图谱（注意，是一类质粒图谱，没关系，照样能找到），直接在搜索框输入pRS，可以看到，之类质粒一共有三十多个。
找到自己需要的质粒名称，点击进入，就可以看到质粒图谱了拿第一个质粒pRS413举例，如上图，质粒图谱是不是很难看，对，我也觉得很难看，没关系，看见view sequence了吗？点击进入，我们就得到该质粒图谱的序列了。
列出三种文献检索工具类型和五种参考工具书类型
列出三种文献检索工具类型和五种参考工具书类型文献检索工具是研究者和学生在进行科学研究和学术写作过程中常用的工具。
它们可用于搜索和查找相关的学术文献和信息资源。
下面将介绍三种常见的文献检索工具类型。
1.图书馆数据库：图书馆数据库是大学图书馆或专业图书馆提供的在线搜索平台，用于查找图书、期刊、报纸、学位论文、技术报告等各类文献资源。
常见的图书馆数据库包括ProQuest、JSTOR、ScienceDirect、PubMed等。
这些数据库覆盖了广泛的学科领域，并提供高质量的学术资源。
用户可以通过关键词搜索、作者搜索、主题搜索等方式，快速定位到所需的学术文献。
2.学术搜索引擎：学术搜索引擎是专门为学术研究者提供的搜索工具，可以搜索全文、期刊文章以及其他学术资源。
学术搜索引擎通过爬取各类学术网站和数据库的内容，构建自己的索引库，用户可以通过输入关键词来进行检索。
常见的学术搜索引擎包括Google学术、Microsoft学术、百度学术等。
它们提供了强大的搜索功能，并且还能够显示文献的被引次数、相关文章、作者信息等，帮助用户更好地了解和使用文献资源。
3.学科专业数据库：学科专业数据库是为特定学科领域而设计的文献检索工具，其收录了该领域的核心期刊、会议论文、专利、技术报告等资源。
学科专业数据库能够提供更加精确和全面的文献搜索结果，帮助研究者深入探索学科前沿。
例如，化学领域的专业数据库有美国化学会（ACS）数据库、维普化学数据库；生物学领域的专业数据库有生物学文摘数据库（BIOSIS Previews）、基因检索数据库（GenBank）等。
参考工具书是指在研究和学习过程中用于查找信息和解决问题的工具书籍。
下面将介绍五种常见的参考工具书类型。
1.百科全书：百科全书是一种系统、全面地收录和阐述知识的工具书，它涵盖了各种学科专业和常识性的知识。
百科全书一般按字母顺序排列内容，并提供详细的解释和相关的辅助资料。
常见的百科全书有《中国大百科全书》、《世界大百科全书》等。
PubMed中文使用手册 (PDF)
PubMed中文使用手册Jeffrey Wu（一）PubMed简介：PubMed是美国家医学图书馆(NLM)下属的国家生物技术信息中心(NCBI)开发的、基于WWW的查询系统。
PubMed是NCBI Entrez 数个数据库查询系统下中的一个。
PubMed 是提供免费的MEDLINE、PREMEDLINE与其他相关数据库接入服务，MEDLINE是一个拥有1亿字条的巨大数据库。
PubMed也包含着与提供期刊全文的出版商网址的链接，来自第三方的生物学数据，序列中心的数据等等。
PubMed提供与综合分子生物学数据库的链接与接入服务，这个数据库归NCBI所有，其内容包括：DNA与蛋白质序列，基因图数据、3D蛋白构象，人类孟德尔遗传在线。
（二）页面介绍:（更新很快，但其内容变化一般不大）在你的浏览器中的URL地址框中健入/pubmed/并单击回车键后，你将进入Pubmed的主页面。
如图：1. 主页面左侧框的介绍（注：Cubby和tutorial为最新加入的）MeSh Browser你可以用它来分层浏览MesH表Single Citation Matcher通过填表的形式输入期刊的信息可以找到某单篇的文献或整个期刊的内容。
Batch Citation Matcher用一种特定的形式输入期刊的信息一次搜索多篇文献。
Clinical Queries这一部分为临床医生设置，通过过滤的方式将搜索的文献固定在4个范围：治疗、诊断、病原学与预后。
Old PubMed (使用以前的PubMed查询方式)关于每一项的具体使用方法, 后面将会有详细介绍。
Related ResourcesOrder Documents提供一种收费性质服务，可以使用户在当地得到文献的全文拷贝（费用与发送方式各不相同）。
Grateful Med是对另一个NLM基于网络的查询系统的链接。
Grateful Med也提供MEDLINE的接入，并且还有一些其他的数据库如AIDSLINE、HISTLINE等等。
PubMed中文使用手册
P u b M e d中文使用手册work Information Technology Company.2020YEARPubMed中文使用手册（一）PubMed简介：PubMed是美国家医学图书馆(NLM)下属的国家生物技术信息中心(NCBI)开发的、基于WWW的查询系统。
PubMed是NCBI Entrez 数个数据库查询系统下中的一个。
PubMed 是提供免费的MEDLINE、PREMEDLINE与其他相关数据库接入服务，MEDLINE是一个拥有1亿字条的巨大数据库。
PubMed也包含着与提供期刊全文的出版商网址的链接，来自第三方的生物学数据，序列中心的数据等等。
PubMed提供与综合分子生物学数据库的链接与接入服务，这个数据库归NCBI所有，其内容包括：DNA与蛋白质序列，基因图数据、3D蛋白构象，人类孟德尔遗传在线。
（二）页面介绍:（更新很快，但其内容变化一般不大）在你的浏览器中的URL地址框中健入/pubmed/并单击回车键后，你将进入Pubmed的主页面。
如图：1. 主页面左侧框的介绍（注：Cubby和tutorial为最新加入的）MeSh Browser你可以用它来分层浏览MesH表Single Citation Matcher通过填表的形式输入期刊的信息可以找到某单篇的文献或整个期刊的内容。
Batch Citation Matcher用一种特定的形式输入期刊的信息一次搜索多篇文献。
Clinical Queries这一部分为临床医生设置，通过过滤的方式将搜索的文献固定在4个范围：治疗、诊断、病原学与预后。
Old PubMed (使用以前的PubMed查询方式)关于每一项的具体使用方法, 后面将会有详细介绍。
Related ResourcesOrder Documents提供一种收费性质服务，可以使用户在当地得到文献的全文拷贝（费用与发送方式各不相同）。
Grateful Med是对另一个NLM基于网络的查询系统的链接。
NCBI资源介绍及使用手册
NCBI资源介绍及使用手册NCBI资源介绍及使用手册1、概述1.1 NCBI简介1.2 NCBI的作用和意义2、NCBI数据库2.1 PubMed2.1.1 检索和浏览文献2.1.2 发表论文的要求和流程2.2 GenBank2.2.1 遗传序列数据的获取和使用2.2.2 序列比对和分析工具的使用2.3 Protein Data Bank（PDB）2.3.1 蛋白质结构数据的检索和浏览 2.3.2 分析蛋白质结构的工具和方法 2.4 Gene Expression Omnibus（GEO）2.4.1 基因表达数据的获取和分析2.4.2 基因表达谱的解读和应用2.5 NCBI BLAST2.5.1 序列比对的基本原理和步骤2.5.2 使用BLAST进行序列比对和注释3、NCBI工具与资源3.1 Primer-BLAST3.1.1 引物设计的基本原理3.1.2 使用Primer-BLAST进行引物设计 3.2 BLAST+3.2.1 BLAST+的功能和特点3.2.2 BLAST+的安装和使用方法3.3 Entrez3.3.1 Entrez数据库的分类和查询方法 3.3.2 使用Entrez进行数据获取和处理 3.4 NCBI Genome Workbench3.4.1 基因组数据的可视化和分析3.4.2 使用Genome Workbench进行基因组研究4、高级应用4.1 NCBI数据挖掘与分析4.1.1 通过NCBI进行序列数据挖掘4.1.2 利用NCBI进行基因组学研究4.2 NCBI数据整合与综合分析4.2.1 结合多个NCBI数据库进行综合分析4.2.2 多种数据源的整合与分析5、附件附件1、NCBI常用工具附件2、实例数据集注释：1、PubMed: 一个由美国国家医学图书馆维护的生物医学文献库，包括了大量的生物医学文献摘要和全文。
2、GenBank: 一个由美国国家生物技术信息中心维护的遗传序列数据库，包含了已知生物学序列的大部分信息。
pubmed文献检索系统使用指南
PubMed医学文献检索系统PubMed是因特网上重要的免费文献检索系统。
目前全球最著名的医学文献数据库系统是美国国立医学图书馆的MEDLINE，该数据库重数据免费提供给各个检索系统的开发商，因此在因特网上有重多的免费MEDLINE检索系统。
这些系统所涵盖的文献年代、检索结果的输出格式以及检索途径各不相同，但是，目前被医务人员广泛使用的仍然是美国国立医学图书馆的PubMed系统PubMed和NCBI：1．美国国立医学图书馆“NLM”2．早在1879年，编译医学文献的检索刊物IM3．1964年采用计算机进行电子编辑和排版，在此基础上开发了“医学文献分析与检索系统”（即著名的MEDLARS）4．1971年正式建立了钙系统的联机系统，称为“MEDLARS联机检索系统，MEDLARS online,既MEDLINE 系统。
5．PubMed则是NLM的国家生物信息中心（National Center for Biotechnology Information, NCBI）开发的一个以网络为基础的检索系统，自1997年免费提供服务PubMed ――特点：PubMed具有MEDLINE 所具有的各种检索和数据库优势，同时还具有以下特点：⏹连接广泛：包括对外链接和对内链接，对内指与NCBI其它数据库的链接和PubMed文献相似度计算后的相关文献链接，对外连接指出版商提供的文献全文的连接，有免费和需要注册的。
⏹更新速度快：出版商直接把电子版提供给NLM⏹收录文献范围广：三个层次的数据库：MEDLINE数据库、PreMEDLINE数据库和出版商直接提供的文献数据库等PubMed ――收录范围总体包括：⏹收录年限：1966～⏹收录内容：70多个国家和地区的4000余种生物医学期刊的文献和一些非医学内容的文献，主要是MEDLINE。
内容涉及医学、护理、牙科、兽医、健康保健系统、前临床医学等学科，另外有非医学内容的文献，如science 和nature中具有地理学方面的文献。
循证医学证据检索
疾病与干预措施组合检索举例
电磁场治疗骨关节炎：
#1
#2 #3 #4 #5 #6 #7 #8
explode "Osteoarthritis"/ all subheadings
osteoarthritis #1 or #2 explode "Electromagnetics"/ all subheadings electromagnetic* explode "Electric-Stimulation-Therapy"/ all subheadings electrical stimulation #4 or #5 or #6 or #7
Osteoarthritis的树状结构
主题词（MeSH）树状结构 TREE 1 of 2: Musculoskeletal Diseases 骨骼肌疾病 Arthritis 关节炎 Osteoarthritis 骨关节炎 Osteoarthritis, Knee 骨关节炎, 膝 Osteoarthritis, Hip 骨关节炎, 髋 Spinal Osteophytosis 脊柱骨赘病 TREE 1 of 2: …… ……
5
基于经验未经严格论证的专家意见
证据级别
高
低
3、证据检索的分类
循证医学实践中证据检索可分为两种：
（1）使用当前最佳证据 如：检索证据用于临床决策参考
（2）利用证据进行相关研究 如：制作系统评价
4、循证医学证据检索的步骤
对循证医学证据进行检索
一般分为5-6个检索步骤
第一步：将临床问题分解为若干要素
（4）信息经评价医学搜索引擎 和一般医学搜索引擎的选择
用通用搜索引擎检索循证医学证据常会 得到大量不相关的检索结果甚至是明显 错误的信息；采用一般的医学专业的搜 索引擎对相关信息进行检索仍不理想
功能磁共振数据分析手册-第1章-翻译版
第1章引言翻译：yingers, nancyxyz, 灵犀校对：Amygdala本书的目的是为读者介绍功能磁共振(fMRI)数据处理和分析的方法及基本原理。
1.1 fMRI简介从20世纪90年代开始，fMRI的发展引起了科学界的轰动。
图1.1所显示的是PubMed数据库中与这一技术相关的生物医学文献数量，从数据增长情况我们可以明显地看到fMRI的发展趋势。
在1996年，仅用一周的时间就可以阅读完所有的fMRI文献；但现在，甚至连前一周发表的文献都读不完。
fMRI技术之所以可以如此快速地发展，得益于它可以比PET更安全而无创伤的获取脑活动成像，并且具有更高的空间和相对较高的时间分辨率。
图1.1. 1992年以来，每年PubMed数据库符合这一查询结果（”fMRI”, “functional MRI” OR “functional magnetic resonance imaging”）的引文数量1.1.1 血流量与神经活动通常使用的fMRI技术所基于的原理是，如果大脑内神经活动增强，相应脑区的血流量就会增加。
这一现象已发现一百多年，但其背后的机制却并不明确。
更有趣的是，对活动脑区的供血量所承载的氧分子要多于活动神经元实际耗氧量。
因此，神经活动引起的血流量增加会带来相关区域血氧含量的提高。
fMRI信号正是取决于血氧水平变化，因而被称为血氧水平依赖信号，即BOLD (Blood Oxygenation Level Dependent)信号。
图1.2展示了一个血液动力学响应的例子，即由短暂神经活动所引起的的血流量的增加。
BOLD fMRI的血液动力学响应有两个主要特点，这两个特点决定了数据的分析方法。
一，血液动力学响应较慢。
神经活动也许仅持续几毫秒，但血流量达到其峰值需要5秒左右，然后在15-20秒返回至基线。
二，血液动力学响应可以大致看作线性非时变系统(Cohen, 1997; Boynton et al., 1996; Dale, 1999)。
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PubMed使用手册【基本查询方法】•一个检索词：一个单词：在文本框中输入检索词，按GO查询。
含两个单词以上的检索词：需要加双引号，注意是英文输入状态下的双引号。
如："ultrasonic diagnosis"是正确的，“ultrasonic diagnosis”是错误的•两个以上的检索词：可使用AND、OR 连接各检索词。
如："three dimensional ultrasound" AND thyroid •可以在“limit”菜单下限制文献出版的时间、语种等等。
【完全手册】PubMed 系统的主要特点1.词汇自动转换功能（Automatic Term Mapping）在PubMed主页的检索提问框中键入检索词，系统将按顺序使用如下4种表或索引，对检索词进行转换后再检索。
（1）MeSH转换表（MeSH Translation Table），包括MeSH词、参见词、副主题词等。
如果系统在该表中发现了与检索词相匹配的词，就会自动将其转换为相应的MeSH词和TextWord词（题名词和文摘词）进行检索。
例如：键入"Vitamin h"，系统将其转换成"Biotin [MeSH Tems] OR Vitamin h [Textword]"后进行检索。
（2）刊名转换表（Journal Tanslation Table），包括刊名全称、MEDLINE 形式的缩写和ISSN号。
该转换表能把键入的刊名全称转换为"MEDLINE缩写[Journal Name]"后进行检索。
如：在检索提问框中键入："new england journal of medicine", PubMed将其转换为"N Engl J Med [Journal Name]"后进行检索。
（3）短语表（Phrase list）。
该表中的短语来自MeSH、含有同义词或不同英文词汇书写形式的统一医学语言系统（UMLS: Unified Medical Language System）和补充概念（物质）名称表[Supplementary Concept (Substance) Name]。
如果PubMed 系统在MeSH和刊名转换表中未发现与检索词相匹配的词，就会查找短词表。
（4）著者索引（Author Index）。
如果键入的词语未在上述各表中找到相匹配的词，或者键入的词是一个后面跟有1~2个字母的短语，PubMed即查著者索引。
如果仍然找不到匹配词，PubMed就会把该词断开后再重复上述自动词汇转换过程，直到找到与键入的词语相匹配词语为止。
若仍然没有匹配词，单个词会被联一起（用AND）在全部字段中检索。
如："single cell"，系统就会自动将其分成两个词："single"和"cell"检索，其检索表达式为："single AND cell"。
要查验检索词的转换情况，可点击"Details"键。
2.截词检索功能PubMed 允许使用"*"号作为通配符进行截词检索。
如：键入"bacter *"，系统会找到那些前一部分是bacter的单词（如bacteria, bacterium, bacteriophage等），并对其分别进行检索。
如果这咱词少于150个，PubMed会逐个词检索，若超过150个（如：Staph*）,PubMed将显示如下警告信息："Wildcard search for 'term*' used only the first 150 variations. Lengthen the root word to search for all endings"。
截词功能只限于单词，对词组无效。
如："infection*"包括"infections"，但不包括"infection control"等。
使用截词功能时，PubMed系统会自动关闭词汇转换功能。
3.强制检索功能如上所述，在PubMed主页的检索提问框中键入一个短语后点击"Go"，系统会高速用自动转换功能查找到相应的匹配词后再进行检索；但是，当键入的词语无匹配词时，PubMed就会将键入的词语断开后再重复上述自动词汇转换过程，若仍然没有匹配词，系统就将短语分解成单词，再用AND联在一起在全部字段中检索。
很明显，这样检索的结果是不符合用户要求的。
因此，PubMed允许使用双引号（""）来强制系统进行短语检索。
例如，在PubMed主页的检索提问框中键入"Single cell"，并用双引号引起来，然后点击"Go"，系统会将其作为一个不可分割的词组在数据库的全部字段中进行检索。
使用双引号检索，会自动关闭词汇转换功能。
4.链接功能（1）链接相关文献。
PubMed系统中的每条文献记录均有一个相关文献链接，在检索结果的显示状态下，每条记录的右边均有"Related Articles"超链。
点击该链，系统按文献的相关度从高到低显示相关文献。
利用检索史（History）按钮能进一步限制相关文献。
点击"History"，把相关检索式的编号录入检索提问框，然后再键入附加条件词，最后点"Go"。
如在检索提问框中键入"#7 AND english[la]"，可将检索进一步限定在英文文献范围内。
（2）链接NCBI（National Center for Biotechnology Information）数据库。
PubMed在其主页上与NCBI的5个数据库建立了超链接。
这些数据库包括：Protein[氨基酸（蛋白质）序列]数据库，Nucleotide(DNA序列)数据库，Popset(种群、种系发生或突变序列)数据库，Structure（分子结构模型）数据库和Genome(基因组序列)数据库。
（3）链接外部资源。
PubMed提供从检索结果到期刊全文、生物学数据、序列中心等的链接。
该功能通过链接上述资源站点的方式来实现。
在检索结果显示状态下，点击"LinkOut"进入相关网站。
（4）链接相关图书。
点击"Books"，可参考相关书籍的文摘页。
书籍文摘页上的某些短语是超链接，点击短语超链，可连到相关图书的页码表，可在表上找到有关短语。
此外，PubMed系统允许用户查看被引期刊名称表，点击主页上的PubMed Journal Brower即可，PubMed向用户提供期刊的缩写名称和ISSN号。
PubMed 检索PubMed系统检索范围：MEDLINE数据库和PreMEDLINE数据库。
1.词语（主题）检索在PubMed主页的提问框中键入英文单词或短语（大写或小写均可后回车或点击"Go"， PubMed即使用其词汇自动转换功能进行检索，并将检索结果直接显示在主页下方。
例如：键入"vitamin c common cold"后回车或点击"Go"， PubMed开始检索并将检索结果显示出来。
如果检索结果不符合要求，可以在提问框中增加或删除词语，或者在Details状态下（参见Details键的用法）来修改检索式，也可使用"Limits"（参见Limits的用法）选择限定条件后再进行检索。
此外，用户可根据需要使用通配符"*"或双引号进行截词检索或强制检索。
2.著者检索在提问框中键入著者姓氏全称和名字的首字母缩写，格式为：著者姓空格名字首字母缩写，例如smith ja，然后回车或点击Go，系统会自动到著者字段去检索，并显示检索结果。
如果在录入了著者的姓氏，系统将首先在MeSH转换表中查找该著者的姓。
查到后，系统检索主题字段和题名与文摘字段，否则，系统将在全部字段中检索。
如果在著者姓名前后使用双引号，并用著者字段标识--[au]加以限定，如"smith ja"[au]，那么系统只检索著者字段。
3.刊名检索在提问框中键入刊名全称或MEDLINE形式的简称、ISSN号，例如：molecular biology of the cell, 或mol biol cell, 或1059-1524，然后回车或点击Go,系统将在刊名字段检索，并显示检索结果。
如果刊名与MeSH词表中的词相同，例如：Gene Therapy、Science或Cell 等，PubMed将把这些词作为MeSH词检索。
在这种情况下，需要用刊名字段标识--[ta]加以限定，如"gene therapy[ ta ]"。
单个词的刊名也需要用[ ta ]限定，如：Scanning[ ta ]。
否则，系统将在全部字段中检索。
使用刊名全称或MEDLINE简称可检索到数据库中的全部相关记录。
使用ISSN号进行检索，则不能保证检到数据库中较早的记录。
若刊名有括号，录入时应将括号省略。
如：J Hand Surg[ Am ]应键入 J Hand Surg Am。
4.布尔逻辑检索PubMed系统允许使用布尔逻辑检索，但要在提问框中键入布尔逻辑运算符（AND，OR或NOT）。
如：vitamin c OR zinc。
布尔逻辑检索的运算顺序为从左至右，但可使用圆括号来改变其运算顺序。
如common cold AND (vitamin c OR zinc), 圆括号中的检索式最先运算。
布尔逻辑检索允许在检索词后附加字段标识以限定检索字段（字段标识要用方括号括起来，位于检索词这后）。
其检索表达式的格式为：检索词[字段标识]布尔运算符检索词[字段标识]。
如：dna[ mh ] AND crick [au ] AND 1993 [ dp ]; 又如：ansthma/therapy[ mh ] AND review[ pt ] AND child, preschool[ mh ]。
各种字段标识见表1。
表1 字段标识一览表字段标识字段名称简要说明AD Affiliation 第一责任者的工作单位、地址，合同号ALL All Fields 全字段AU Author Name 著者姓名RN EC/RN Number 酶学委员会分配给特定酶的编号和化学文献社的登记号EDAT Entrez Date 录入PubMed系统数据库的日期FILTER Filter 由PubMed系统链接的外部资源站点所使用的用来限定文献的技术标识 IP Issue 期刊的期号TA Journal Title 期刊名称或IISN号LA Language 语言文种MHDA MeSH Date 标引MeSH主题词的日期MAJR MeSH Major Topic 主要MeSH 主题词MH MeSH Terms 全部MeSH主题词PG Page Number 期刊页码PS Personal Name as Subject 人名主题词DP Publication Date 文献出版日期PT Publication Type 文献类型，包括综述、临床试验、通信等SHP Subheadings MeSH副主题词SI Secondary source ID 用于限定检索与PubMed系统中的文献条目相关的分子序列资源数据库（如Genbank[ si ]）和/或该数据库中的存取号（如：AF001892[ si ]）SB Subset 用于限定检索PubMed下属的文献数据库（包括MEDLINE，PreMEDLINE, Publisher和AIDS数据库）。