Manninotriose_HNMR_25782_MedChemExpress
莫博赛替尼化学结构
莫博赛替尼化学结构全文共四篇示例，供读者参考第一篇示例：莫博赛替尼（Imatinib，商品名格列卫）是一种靶向治疗白血病的药物，也被用于治疗一些其他类型的癌症。
它是通过靶向特定的蛋白质，从而阻断癌细胞的生长和扩散。
莫博赛替尼的化学结构是一种非常复杂的有机分子，其分子式为C29H31N7O，分子量为493.604克/摩尔。
莫博赛替尼的化学结构包含一个核心环结构，由苯环和嘧啶环连接而成。
苯环是由六个碳原子和六个氢原子组成的环状结构，而嘧啶环是由一个氮原子和四个碳原子组成的环状结构。
这两个环通过一个氮原子相连，形成了一种特殊的结构，这种结构对于莫博赛替尼的药效非常重要。
莫博赛替尼在体内主要靶向作用于一种叫做BCR-ABL融合蛋白的蛋白质。
这种融合蛋白质是一种异常的蛋白质，由Bcr（一种信号传导蛋白）和Abl（一种酪氨酸激酶）两种蛋白质的部分结构融合而成。
这种异常蛋白质的产生是由于某些白血病细胞的染色体发生了特定的基因突变，导致Bcr和Abl两种基因相互融合。
而莫博赛替尼正是针对这种异常的蛋白质进行靶向治疗的。
莫博赛替尼的化学结构设计和药效机制是经过长期的研究和开发的。
科学家们通过不断的实验和研究，逐渐了解了白血病细胞的基因突变以及融合蛋白质的结构和功能特点。
通过对这些信息的深入研究，他们最终设计出了莫博赛替尼这种能够精准干预癌细胞生长的药物。
莫博赛替尼在临床应用中被证实具有显著的疗效，尤其是对于慢性髓细胞白血病（CML）和胃肠间质瘤（GIST）等罕见白血病和恶性肿瘤的治疗效果非常显著。
通过连续服用莫博赛替尼，患者的白血细胞数量可以得到控制，进而延缓疾病的进展并提高生存率。
莫博赛替尼的治疗效果和安全性已经得到了许多临床试验和长期随访的验证，被广泛应用于临床治疗。
莫博赛替尼是一种非常重要的抗癌药物，通过靶向作用于异常蛋白质来抑制癌细胞的生长和扩散。
其化学结构复杂且精确，对于白血病和其他类型的癌症具有显著的治疗效果。
中药墨旱莲中的三萜皂苷_英文_
Journal of Chinese Pharmaceutical Sciences 2001, 10 (4)183Triterpenoid Saponins from Eclipta prostrata L.*Tang Haifeng 1, Zhao Yueping 1, Jiang Yongpei 1, Wang Zhongzhuang 2, Yi Yanghua 3 and Lei Qiyun 11. Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an 710032;2. Changhai Hospital, Second Military Medical University, Shanghai 200433;3. College of Pharmacy, Second Military Medical University, Shanghai 200433Received October 20, 2001; Accepted November 2, 2001Abstract Five triterpenoid saponins were isolated from the Chinese traditional medicine Eclipta prostrataL.. On the basis of their chemical properties and spectral data, they were identified as eclalbasaponins II(1), I(2), III(3), 3-O-[β-D -glucopyranosyl(1→2)-β-D -glucopyranosyl]-16α-ethoxy-olean-12-ene-28-oic acid-28-O-β-D -glu-copyranoside(4) and 3-O-[(2-O-sulfuryl-β-D -glucopyranosyl)(1→2)-β-D -glucopyranosyl]-echinocystic acid-28-O-β-D -glucopyranoside(5). Compounds 4 and 5 are new compounds and named eclalbasaponins XI and XII, respectively. Compounds 1 and 5 induced morphological deformation of Pyricularia oryzae mycelia.Key words Eclipta prostrata ; Eclalbasaponin XI; Eclalbasaponin XII; Pyricularia oryzae ; BioassayIntroductionThe dried aerial parts of Eclipta prostrata L. (Com-positae) known as ‘Mo Han Lian” in Chinese traditional medicine, has been used for the treatment of haemor-rhage, hepatitis and coronary artery disease, etc.. It has been reported that the methanol extract exhibited signifi-cant antitumor activity. Triterpenoid saponins, thiophene acetylenes and coumestans have been isolated from the title plant [1]. In order to find new bioactive agents, we investigated the constituents of the materials with Pyricularia oryzae bioassay-guided fractionation method. From the methanol extract of the crude drug two new compounds, eclalbasaponins XI (4) and XII (5), together with three known saponins, eclalbasaponins II (1), I (2) and III (3) were isolated and identified.1 R 1=H R 2=H R 3=H2 R 1=H R 2=Glc R 3=H3 R 1=Glc R 2=Glc R 3=H4 R 1=GlcR 2=Glc R 3=CH 2CH 3 5R 1=(2′-O-SO 3H)Glc R 2=Glc R 3=HFig. 1. Structures of saponins 1-5.Results and DiscussionEclalbasaponins II, I and III (1~3) were identified by comparison of their physical and spectral data with thoseof authentic samples [2].Eclalbasaponin XI (4) was obtained as a colorless crystalline powder. The IR, MS, 1H NMR and 13C NMR data indicated that it might have an olean-12-ene pentacyclic triterpene skeleton. Its molecular formula was established to be C 50H 82O 19 based on elemental analysis and FAB-MS, indicating that 4 has one more C 2H 4 group than 3. With acid hydrolysis, 4 yielded only D -glucose as sugar component and an aglycone 4a , its EI-MS m/z: 500(M +), 485[M-CH 3]+, 455[M-OCH 2CH 3]+, 292(fragment ion a), 246(a-C 2H 5OH), 208(fragment ion b), 207, indicated that the molecular weight of 4a was twenty -eight more than 3a , which is the aglycone of 3. The 13C and 1H NMR spectra of 4 exhibited eighteen carbon and three anomeric proton signals attributable to three glucopyranosyl residues, whose chemical shifts were identical to those of 3. These results showed that the linkage sequence and position of the glucopyranosyl unit and the aglycone skeleton of 4 were identical with those of 3, the only difference was the presence of one more C 2H 4 group attached to the aglycone of 4. Spectral comparison of 4 with 3 revealed that 4 exhibited, in addition, two other proton signals at δ 1.25(3H, t, J=7.0 Hz), 3.81(2H, q, J=7.0 Hz) and two other carbon signals at δ 56.1(CH 2) and 17.9(CH 3). Meanwhile, the C-16 signal (δ 75.8) of 4 was shifted downfield by 2.7, indi-cating that the ethoxy group was linked to C-16 position. The one-proton singlet at δ 5.07 due to 16-H suggested the 16-OC 2H 5 should be the α-configuration, since the aa and ae coupling relationships of 16-H with 15α- and 15β-H were not observed. Full assignments of the 1H and 13C signals of 4 were secured by the HMQC and HMBC spectra. In the HMBC spectrum, the methylene proton signal of the ethoxy group (δ 3.81) showed*First published in Chinese in Acta Pharmaceutica Acta, 2001, 36: 660.O O OHOH HO1OR 3COOR 2correlations with the carbon signals at δ 17.9 (methyl of the ethoxy group) and 75.8(C-16); the 16-H and methyl proton signals at δ 5.07 and 1.25 all showed correlations with the methylene carbon signal of ethoxy group at δ56.1; the anomeric proton signal at δ 4.86 and the 3-H signal at δ 3.23 showed correlations with carbon signals at δ 87.8(C-3) and 103.7(Glc C-1), respectively. Based on the above evidence, the structure of 4 was established as 3-O-[β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-16α-etho xy-olean-12-ene-28-oic acid-28-O-β-D-glucopyranoside.Eclalbasaponin XII (5) was obtained as white amor-phous powder, which showed a [M-H+2Na]+ peak at m/z 1083.4414(C48H77Na2O22S) in the HR-FAB-MS. Acid hydrolysis of 5 liberated D-glucose and echinocystic acid. Solvolysis using dioxane-pyridine afforded prosapogenin 5b, FAB-MS m/z 997[M+K]+, 981[M+Na]+, 819[M-Glc+Na]+. The 1H and 13C NMR spectra of 5b were identical with those of3, consequently, 5b was elucidated as 3. This evidence established that 5 was a sulfated derivative of 3. On comparative study of the 13C NMR data of 5 with that of 3, the aglycone moiety was identical except for the C-1′(-2.5), C-2′(+5.6) and C-3′(-0.7) of the terminal glucosyl moiety due to sulfation shifts[3]. The HMQC spectrum of 5 the C-2′ signal of the terminal glucose at δ 81.4 correlated with the 1H NMR signal at δ 5.03(2′-H), while the HMQC spectrum of 4 showed that the 2′-H signal of the terminal glucose was at about δ 4.1. These experiments indicated that the sul-fate group should be located at the C-2′ of the ter-minal glucose in 5. Therefore, the structure of 5 was elucidated as 3-O-[2-O-sulfuryl-β-D-glucopyrano-syl] (1→2)-β-D-glucopyranosyl]-echinocystic acid-28-O-β-D-glucopyranoside. Saponins with a sulfate group have rarely been isolated from the plant kingdom. Yahara et al have reported the isolation of sulfated derivatives of saponins 1 and 2 from E. prostrata collected in Japan and purchased in Nanjing. Nevertheless, no sulfated saponins were obtained from the materials purchased in Anguo, Hebei Province according to chemical studies carried out by Zhang et al.[4,5]. Whether the existing of this kinds of compounds have relationship with their growing area remain to be further investigated.Pyricularia oryzae P-2b, a plant pathogenic fungus, has been used as a test microorganism for the primary screening of antineoplastic and antifungal agents such as rhizoxin, fusarielin A from natural sources[6]. We applied the bioassay method as a guide to search for the active fraction of E. prostrata. The evaluation data showed that saponins 1 and 5 exhibited activities causing morpho-logical abnormality of P. oryzae mycelia and the mini-mum morphological deformation concentration (MMDC) were 197 and 30 µmol⋅L-1, respectively. Further antitu-mor screening is still in progress.ExperimentalMelting points were determined on a micromelting point apparatus and were uncorrected. IR spectra in KBr were obtained on a Hitachi 275-50 spectrometer. NMR spectra were recorded on Bruker-spectrospin AC-300P and Varian Inova-400 spectrometer using TMS as inter-nal standard. MOD-1106 apparatus was used for ele-mental analysis. HPLC was carried out with a Zorbax C18 ODS column (9.4 mm × 250 mm) using a SPD-M10Avp PAD UV detector. Silica gel (100~200 mesh) was used for column chromatography. TLC was performed on precoated HSGF254 silica gel plates and detection was achieved by spraying with 20% H2SO4 fol-lowed by heating.Plant materialsThe crude drug was purchased in Shanghai in June, 1997, and identified as the aerial parts of Eclipta pros-trata by Dr. Wang Zhongzhuang. Voucher specimens were deposited in College of Pharmacy, Second Military Medical University, Shanghai.IsolationThe dry crude drug 3.6 kg was extracted three times with EtOH under reflux. After removal of solvent, the residue was extracted repeated with MeOH and the ex-tract (480 g) was partitioned between benzene, EtOAc, n-BuOH and H2O. The EtOAc phase was removed to furnish the residue (30 g), twenty grams of which was subjected to column chromatography on silica gel eluted with CHCl3-MeOH (15:1→8:1→3:1), to provide 13 fractions (Fr. 1~Fr. 13). Fr. 6, Fr. 9 and Fr. 11 which proved to be more active against P. oryzae were further separated by rechromatography on silica gel and prepa-rative HPLC (MeOH-H2O=3:2~4:1), respectively, af-fording saponins 1 (2260 mg), 2 (620 mg), 3 (135 mg), 4 (25 mg) and 5 (48 mg).Structure elucidationSaponin 1 colorless crystalline powder, mp 233~ 234 o C, Liebermann-Burchard and Molish reaction (+). IR (KBr) cm-1: 3425(OH), 1695(COOH), 1625(C=O). FAB-MS m/z: 673[M+K]+, 657[M+Na]+, 455[M-Glc-OH]+. Anal. Found (%): C 68.10, H 9.26; C36H58O9 requires(%): C 68.13, H 9.14. 1H NMR (300 MHz, C5D5N) δ: 0.83, 0.96, 0.99, 1.03, 1.15, 1.25, 1.83(each 3H, s, 7×CH3), 3.38(1H, m, 18-H), 3.58(1H, brd, J=10.2 Hz, 3-H), 4.91(1H, d, J=7.6 Hz, Glc 1-H), 5.22(1H, brs, 16-H), 5.61(1H, brs, 12-H). 13C NMR: see Table 1.Journal of Chinese Pharmaceutical Sciences 2001, 10 (4) 185 Table 1. 13C NMR spectral data of saponins 1~5.C 1 2 3 4 5 C 1 2 3 4 51 38.7 38.8 37.8 37.6 37.8 27 27.2 27.2 26.2 26.0 26.22 26.5 26.5 25.4 25.3 25.4 28 179.9 175.9 174.9 174.7 174.93 88.7 88.8 87.9 87.8 88.4 29 33.2 33.1 32.0 31.9 32.24 39.4 39.4 38.3 38.2 38.6 30 24.7 24.6 23.6 23.3 23.55 55.8 55.9 54.8 54.7 54.8 OCH2CH356.16 18.4 18.5 17.4 17.3 17.4 OCH2CH317.97 33.4 33.4 32.3 32.2 32.4 3-O-Glc8 39.8 40.1 38.8 38.8 39.0 1 106.7 106.8 103.8 103.7 103.99 47.1 47.1 46.0 45.9 46.1 2 75.7 75.7 82.0 81.9 82.210 36.9 37.0 35.7 35.7 35.9 3 78.6 79.2 77.4 77.3 77.511 23.7 23.8 22.6 22.6 22.7 4 71.7 71.8 70.6 70.4 70.712 122.3 122.6 121.6 121.4 121.9 5 78.1 78.7 77.0 76.9 77.213 145.0 144.4 143.4 143.2 143.5 6 62.9 63.0 61.6 61.4 61.614 42.0 42.0 40.9 40.8 41.0 1′104.8 104.6 102.315 36.0 36.1 34.9 34.7 34.9 2′75.8 75.8 81.416 74.6 74.3 73.1 75.8 73.3 3′77.2 77.1 76.517 48.8 49.1 48.2 47.9 48.2 4′70.6 70.4 70.718 41.3 41.3 40.1 40.1 40.2 5′76.8 76.6 76.819 47.2 47.1 46.0 45.9 46.1 6′61.6 61.4 61.620 30.9 30.8 29.6 29.6 29.8 28-O-Glc21 36.0 35.9 34.9 34.9 35.0 1 95.8 94.8 94.6 94.722 32.7 32.1 31.0 31.0 31.2 2 74.1 73.0 72.9 73.023 28.2 28.2 27.0 26.9 27.2 3 78.8 78.3 78.1 78.324 17.0 17.0 15.8 15.6 16.0 4 71.1 70.1 69.8 70.025 15.1 15.6 14.5 14.4 14.5 5 78.2 77.7 77.5 77.726 17.4 17.5 16.3 16.3 16.5 6 62.2 61.2 60.9 61.2 The spectra of 1 and 2 were recorded in C5D5N, while 3, 4 and 5 recorded in C5D5N-D2O.Saponin 2 colorless crystalline powder, mp 250~ 252 o C. Liebermann-Burchard and Molish reaction (+). IR(KBr)cm-1: 3430(OH), 1735(COOR), 1625(C=C), 1080, 1025(C-O). FAB-MS m/z: 835[M+K]+, 819 [M+ Na]+, 455[M-2Glc-OH]+, 437[M-2Glc-OH-H2O]+. Anal. Found(%): C 63.48, H 8.62; C42H68O14 requires(%): C 63.31, H 8.54. 1H NMR (300 MHz, C5D5N) δ: 0.85, 0.97, 0.97, 1.01, 1.10, 1.25, 1.81(each 3H, s, 7×CH3), 3.37(1H, m, 18-H), 3.48(1H, brd, J=9.9 Hz, 3-H), 4.90(1H, d, J=7.7 Hz, Glc 1-H), 5.27(1H, brs, 16-H), 5.58(1H, brs, 12-H), 6.28(1H, d, J=8.0 Hz, 28-O-Glc 1-H). 13C NMR: see Table 1.Saponin 3 colorless crystalline powder, mp 235o C (dec.). Liebermann-Burchard and Molish reaction (+). IR(KBr) cm-1: 3450(OH), 1740(COOR), 1630(C=C), 1080, 1035(C-O). FAB-MS m/z 997[M+K]+, 981[M+ Na]+, 819[M-Glc+Na]+. Anal. Found(%): C 60.59, H 8.17; C48H78O19 requires(%): C 60.12, H 8.14. 1H NMR (400 MHz, C5D5N-D2O) δ: 0.83, 0.97, 1.00, 1.06, 1.09, 1.22, 1.79(each 3H, s, 7×CH3), 3.25(1H, m, 18-H), 3.42(1H, brd, J=11.0 Hz, 3-H), 4.87(1H, d, J=7.5 Hz, Glc 1-H), 5.30(1H, brs, 16-H), 5.33(1H, d, J=7.5 Hz, Glc 1′-H), 5.58(1H, brs, 12-H), 6.30(1H, d, J=8.0 Hz, 28-O-Glc 1-H). 13C NMR: see Table 1.Saponin 4 colorless crystalline powder, mp 231~ 233o C (dec.). Liebermann-Burchard and Molish reaction (+). IR(KBr) cm-1: 3420(OH), 1735(COOR), 1630(C=C), 1080, 1030(C-O). FAB-MS m/z: 1025[M+K]+, 1009 [M+Na]+, 847[M-Glc+Na]+. Anal. Found(%): C 61.08, H 8.36; C50H82O19 requires(%): C 60.85, H 8.32. 1H NMR (400 MHz, C5D5N-D2O) δ: 0.82, 0.95, 0.99, 1.04, 1.08, 1.20, 1.78(each 3H, s, 7×CH3), 1.25(3H, t, J=7.0 Hz, -OCH2CH3), 3.23(1H, m, 18-H), 3.45(1H, brd, J=10.8 Hz, 3-H), 3.81(2H, q, J=7.0 Hz, -OCH2CH3), 4.86(1H, d, J=7.5 Hz, Glc 1-H), 5.07(1H, brs, 16-H), 5.33(1H, d, J=7.6 Hz, Glc 1′-H), 5.56(1H, brs, 12-H), 6.28(1H, d, J=8.1 Hz, 28-O-Glc 1-H). 13C NMR: see Table 1.Saponin 5 colorless amorphous powder, mp 235~ 237o C (dec.). Liebermann-Burchard and Molish reaction (+). IR(KBr) cm-1: 3430(OH), 1740(COOR), 1630(C=C), 1080, 1030(C-O). HR-FAB-MS m/z: 1083.4414{[M-H+ 2Na]+, C48H77Na2O22S requires 1083.4423}. 1H NMR (400 MHz, C5D5N-D2O) δ: 0.82, 0.98, 1.03, 1.10, 1.13, 1.36, 1.81(each 3H, s, 7×CH3), 3.24(1H, m, 18-H), 3.39(1H, brd, J=10.9 Hz, 3-H), 4.92(1H, d, J=7.6 Hz, Glc 1-H), 5.31(1H, brs, 16-H), 5.38(1H, d, J=7.5 Hz, Glc 1′-H), 5.57(1H, brs, 12-H), 6.30(1H, d, J=8.0 Hz, 28-O-Glc 1-H). 13C NMR: see Table 1.Acid hydrolysis of 1~5A solution of each sample (3 30 mg, 4 5 mg, 1, 2 and 5 each 1~2 mg) in 1 mol⋅L-1 HCl-50% MeOH wasrefluxed at 80o C for 4 h. The reaction mixtures were diluted with H2O and extracted with CHCl3. The aqueous layers were concentrated and subjected to HPTLC analysis, and all showed the presence of glucose. Each CHCl3 extract was chromatographed on a silica gel column with n-hexane-acetone (4:1) as eluent to give 3a 6 mg, 4a 1 mg, 1a 2a and 5a (trace), respectively. 3a was obtained as colorless crystalline powder. EI-MS m/z: 472(M+), 454[M-N2O]+, 439, 264, 246, 208. 1H NMR (300 MHz, C5D5N) δ: 0.91, 1.01, 1.04, 1.06, 1.15, 1.25, 1.83(each 3H, s, 7×CH3), 3.37(1H, m, 18-H), 3.60(1H, brd, J=10.8 Hz, 3-H), 5.22(1H, brs, 16-H), 5.63(1H, brs, 12-H). Based on the above data, 3a was determined to be echinocystic acid. Compound 4a white crystalline pow-der, EI-MS m/z: 500, 485, 455, 292, 246, 208, 207. On HPTLC, 1a, 2a, 5a and 3a showed the identical R f val-ues.Alkaline hydrolysis of 3Saponin 3 (50 mg) was refluxed at 60o C with 1 mol⋅L-1 NaOH solution for 2 h. After neutralizationwith 1 mol⋅L-1 HCl solution, the reaction mixture was separated on a silica gel column using CHCl3-MeOH-H2O (14:6:1) as eluting solvent to yield prosapogenin 3b 18 mg, FAB-MS m/z 819[M+Na]+,455[M-2Glc-OH]+. The 1H and 13C NMR data of 3bwere identical with those of eclalbasaponin IV, a known saponin[2].Solvolysis of 5A solution of 5 (20 mg) in dioxane-pyridine (1 : 1,10 mL) was kept at 140 o C in a sealed tube for 3 h. The mixture was evaporated under a N2 and chromato-graphed on a silica gel column (CHCl3-MeOH-H2O=13:7:2, lower layer) to afford prosapogenin 5b 7 mg,FAB=MS m/z 997, 981, 819. The 1H and 13C NMR dataof 5b were identical with those of 3.Acknowledgement We are grateful to Prof. Yao Xinsheng of Shenyang Pharmaceutical University for his technical assistance of P. oryzae bioassay.References[1] Tang HF, Zhao YP, Jiang YP. [J] Northwert Pharm J, 1999, 14: 32[2] Yahara S, Ding N, Nohara T. [J] Chem Pharm Bull, 1994, 42: 1336[3] Yahara S, Ding N, Nohara T, Masuda K, Ageta H. [J] Phytochemistry, 1997, 44: 131[4] Zhang M, Chen YY. [J] Acta Pharm Sin, 1996, 31: 196[5] Zhang M, Chen YY, Di XH, Liu M. [J] Acta Pharm Sin, 1997, 32: 633[6] Kobayashi H, Namikoshi M, Yoshimoto T, Yokochi T. [J] J Antibiot, 1996, 49: 873中药墨旱莲中的三萜皂苷汤海峰１ 赵越平１ 蒋永培１ 王忠壮２ 易杨华３ 雷其云１ 1. 第四军医大学西京医院药剂科，西安710032；2. 第二军医大学长海医院，上海200433；3. 第二军医大学药学院，上海200433摘要从中药墨旱莲Eclipta prostrata L. 中分离得到5个三萜皂苷，根据理化性质和光谱数据，分别鉴定为eclalbasaponins II (1), I (2), III (3), 3-O-[β-D-吡喃葡糖(1→2)-β-D-吡喃葡糖]-16α-乙氧基-齐墩果酸-28-O-β-D-吡喃葡糖苷(4) 和3-O-[(2-O-硫酰基-β-D-吡喃葡糖)(1→2)-β-D-吡喃葡糖]-刺囊酸-28-O-β-D-吡喃葡糖苷(5)。
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刊名简称刊名全称ATMOS CHEM PHYS ATMOSPHERIC CHEMISTRY AND PHYSICSB AM METEOROL SOC BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY CLIM DYNAM CLIMATE DYNAMICSCONTRIB MINERAL PETR CONTRIBUTIONS TO MINERALOGY AND PETROLOGY EARTH PLANET SC LETT EARTH AND PLANETARY SCIENCE LETTERSEARTH-SCI REV EARTH-SCIENCE REVIEWSGEOCHIM COSMOCHIM AC GEOCHIMICA ET COSMOCHIMICA ACTAGEOLOGY GEOLOGYGEOTEXT GEOMEMBRANES GEOTEXTILES AND GEOMEMBRANESJ CLIMATE JOURNAL OF CLIMATEJ PETROL JOURNAL OF PETROLOGYLIMNOL OCEANOGR LIMNOLOGY AND OCEANOGRAPHYNAT GEOSCI Nature GeosciencePALEOCEANOGRAPHY PALEOCEANOGRAPHYPRECAMBRIAN RES PRECAMBRIAN RESEARCHQUATERNARY SCI REV QUATERNARY SCIENCE REVIEWSREV GEOPHYS REVIEWS OF GEOPHYSICSGEOPHYS RES LETT GEOPHYSICAL RESEARCH LETTERSJ ATMOS SCI JOURNAL OF THE ATMOSPHERIC SCIENCESJ GEOPHYS RES JOURNAL OF GEOPHYSICAL RESEARCHJ HYDROL JOURNAL OF HYDROLOGYMON WEATHER REV MONTHLY WEATHER REVIEWANNU REV ASTRON ASTR ANNUAL REVIEW OF ASTRONOMY AND ASTROPHYSICS ASTRON ASTROPHYS REV ASTRONOMY AND ASTROPHYSICS REVIEWASTROPHYS J SUPPL S ASTROPHYSICAL JOURNAL SUPPLEMENT SERIES ASTROPHYS J ASTROPHYSICAL JOURNALACM COMPUT SURV ACM COMPUTING SURVEYSACM T GRAPHIC ACM TRANSACTIONS ON GRAPHICSACS NANO ACS NanoACTA BIOMATER Acta BiomaterialiaACTA MATER ACTA MATERIALIAADV APPL MECH ADVANCES IN APPLIED MECHANICSADV BIOCHEM ENG BIOT ADVANCES IN BIOCHEMICAL ENGINEERING / BIOTECHNOL ADV FUNCT MATER ADVANCED FUNCTIONAL MATERIALSADV MATER ADVANCED MATERIALSANNU REV BIOMED ENG ANNUAL REVIEW OF BIOMEDICAL ENGINEERINGANNU REV MATER RES ANNUAL REVIEW OF MATERIALS RESEARCHAPPL SPECTROSC REV APPLIED SPECTROSCOPY REVIEWSARTIF INTELL ARTIFICIAL INTELLIGENCEBIOMATERIALS BIOMATERIALSBIORESOURCE TECHNOL BIORESOURCE TECHNOLOGYBIOSENS BIOELECTRON BIOSENSORS & BIOELECTRONICSBIOTECHNOL ADV BIOTECHNOLOGY ADVANCESBIOTECHNOL BIOENG BIOTECHNOLOGY AND BIOENGINEERINGBIOTECHNOL BIOFUELS Biotechnology for BiofuelsCARBON CARBONCHEM MATER CHEMISTRY OF MATERIALSCOMPUT INTELL COMPUTATIONAL INTELLIGENCECRIT REV BIOTECHNOL CRITICAL REVIEWS IN BIOTECHNOLOGYCRIT REV FOOD SCI CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION CURR OPIN BIOTECH CURRENT OPINION IN BIOTECHNOLOGY ELECTROCHEM COMMUN ELECTROCHEMISTRY COMMUNICATIONSHUM-COMPUT INTERACT HUMAN-COMPUTER INTERACTIONIEEE J SEL AREA COMM IEEE JOURNAL ON SELECTED AREAS IN COMMUNICATIONS IEEE SIGNAL PROC MAG IEEE SIGNAL PROCESSING MAGAZINEIEEE T EVOLUT COMPUT IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION IEEE T IND ELECTRON IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS IEEE T NEURAL NETWOR IEEE TRANSACTIONS ON NEURAL NETWORKSIEEE T PATTERN ANAL IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHIN IEEE T SOFTWARE ENG IEEE TRANSACTIONS ON SOFTWARE ENGINEERINGINT J COMPUT VISION INTERNATIONAL JOURNAL OF COMPUTER VISIONINT J HYDROGEN ENERG INTERNATIONAL JOURNAL OF HYDROGEN ENERGYINT J NONLIN SCI NUM INTERNATIONAL JOURNAL OF NONLINEAR SCIENCES AND INT J PLASTICITY INTERNATIONAL JOURNAL OF PLASTICITYINT MATER REV INTERNATIONAL MATERIALS REVIEWSJ CATAL JOURNAL OF CATALYSISJ HAZARD MATER JOURNAL OF HAZARDOUS MATERIALSJ MATER CHEM JOURNAL OF MATERIALS CHEMISTRYJ MECH BEHAV BIOMED Journal of the Mechanical Behavior of Biomedical J NEURAL ENG Journal of Neural EngineeringJ POWER SOURCES JOURNAL OF POWER SOURCESJ WEB SEMANT Journal of Web SemanticsLAB CHIP LAB ON A CHIPMACROMOL RAPID COMM MACROMOLECULAR RAPID COMMUNICATIONS MACROMOLECULES MACROMOLECULESMAT SCI ENG R MATERIALS SCIENCE & ENGINEERING R-REPORTS MATER TODAY Materials TodayMED IMAGE ANAL MEDICAL IMAGE ANALYSISMETAB ENG METABOLIC ENGINEERINGMIS QUART MIS QUARTERLYMOL NUTR FOOD RES MOLECULAR NUTRITION & FOOD RESEARCHMRS BULL MRS BULLETINNANO LETT NANO LETTERSNANO TODAY Nano TodayNANOMED-NANOTECHNOL Nanomedicine-Nanotechnology Biology and Medicine NANOTECHNOLOGY NANOTECHNOLOGYNAT BIOTECHNOL NATURE BIOTECHNOLOGYNAT MATER NATURE MATERIALSNAT NANOTECHNOL Nature NanotechnologyORG ELECTRON ORGANIC ELECTRONICSP IEEE PROCEEDINGS OF THE IEEEPLASMONICS PlasmonicsPOLYM REV Polymer ReviewsPROG CRYST GROWTH CH PROGRESS IN CRYSTAL GROWTH AND CHARACTERIZATION PROG ENERG COMBUST PROGRESS IN ENERGY AND COMBUSTION SCIENCEPROG MATER SCI PROGRESS IN MATERIALS SCIENCEPROG PHOTOVOLTAICS PROGRESS IN PHOTOVOLTAICSPROG QUANT ELECTRON PROGRESS IN QUANTUM ELECTRONICSPROG SURF SCI PROGRESS IN SURFACE SCIENCERENEW SUST ENERG REV RENEWABLE & SUSTAINABLE ENERGY REVIEWSSMALL SMALLSOFT MATTER Soft MatterTRENDS BIOTECHNOL TRENDS IN BIOTECHNOLOGYTRENDS FOOD SCI TECH TRENDS IN FOOD SCIENCE & TECHNOLOGYVLDB J VLDB JOURNALAICHE J AICHE JOURNALAPPL MICROBIOL BIOT APPLIED MICROBIOLOGY AND BIOTECHNOLOGYCHEM ENG SCI CHEMICAL ENGINEERING SCIENCEELECTROCHIM ACTA ELECTROCHIMICA ACTAFOOD CHEM FOOD CHEMISTRYIEEE T ANTENN PROPAG IEEE TRANSACTIONS ON ANTENNAS AND PROPAGATION IEEE T AUTOMAT CONTR IEEE TRANSACTIONS ON AUTOMATIC CONTROLIEEE T INFORM THEORY IEEE TRANSACTIONS ON INFORMATION THEORYIEEE T MICROW THEORY IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNI IEEE T SIGNAL PROCES IEEE TRANSACTIONS ON SIGNAL PROCESSINGIND ENG CHEM RES INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCHINT J HEAT MASS TRAN INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER J AM CERAM SOC JOURNAL OF THE AMERICAN CERAMIC SOCIETYJ ELECTROCHEM SOC JOURNAL OF THE ELECTROCHEMICAL SOCIETYJ MEMBRANE SCI JOURNAL OF MEMBRANE SCIENCEMATER LETT MATERIALS LETTERSSCRIPTA MATER SCRIPTA MATERIALIASENSOR ACTUAT B-CHEM SENSORS AND ACTUATORS B-CHEMICALSURF COAT TECH SURFACE & COATINGS TECHNOLOGYSYNTHETIC MET SYNTHETIC METALSTHIN SOLID FILMS THIN SOLID FILMSJ OPER MANAG JOURNAL OF OPERATIONS MANAGEMENTMANAGE SCI MANAGEMENT SCIENCEOMEGA-INT J MANAGE S OMEGA-INTERNATIONAL JOURNAL OF MANAGEMENT SCIENC PROD OPER MANAG PRODUCTION AND OPERATIONS MANAGEMENTEUR J OPER RES EUROPEAN JOURNAL OF OPERATIONAL RESEARCH ACCOUNTS CHEM RES ACCOUNTS OF CHEMICAL RESEARCHACTA CRYSTALLOGR A ACTA CRYSTALLOGRAPHICA SECTION AALDRICHIM ACTA ALDRICHIMICA ACTAANGEW CHEM INT EDIT ANGEWANDTE CHEMIE-INTERNATIONAL EDITIONANNU REV PHYS CHEM ANNUAL REVIEW OF PHYSICAL CHEMISTRYCATAL REV CATALYSIS REVIEWS-SCIENCE AND ENGINEERINGCHEM REV CHEMICAL REVIEWSCHEM SOC REV CHEMICAL SOCIETY REVIEWSCOORDIN CHEM REV COORDINATION CHEMISTRY REVIEWSENERG ENVIRON SCI Energy & Environmental ScienceINT REV PHYS CHEM INTERNATIONAL REVIEWS IN PHYSICAL CHEMISTRYJ AM CHEM SOC JOURNAL OF THE AMERICAN CHEMICAL SOCIETYJ PHOTOCH PHOTOBIO C JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY C-PHO NAT PROD REP NATURAL PRODUCT REPORTSPROG POLYM SCI PROGRESS IN POLYMER SCIENCESURF SCI REP SURFACE SCIENCE REPORTSTRAC-TREND ANAL CHEM TRAC-TRENDS IN ANALYTICAL CHEMISTRYANAL CHEM ANALYTICAL CHEMISTRYJ ORG CHEM JOURNAL OF ORGANIC CHEMISTRYJ PHYS CHEM B JOURNAL OF PHYSICAL CHEMISTRY BLANGMUIR LANGMUIRAPPL CATAL B-ENVIRON APPLIED CATALYSIS B-ENVIRONMENTALB AM MUS NAT HIST BULLETIN OF THE AMERICAN MUSEUM OF NATURAL HISTO CRIT REV ENV SCI TEC CRITICAL REVIEWS IN ENVIRONMENTAL SCIENCE AND TE ECOL LETT ECOLOGY LETTERSECOL MONOGR ECOLOGICAL MONOGRAPHSECOLOGY ECOLOGYENVIRON HEALTH PERSP ENVIRONMENTAL HEALTH PERSPECTIVESENVIRON MICROBIOL ENVIRONMENTAL MICROBIOLOGYEVOLUTION EVOLUTIONFRONT ECOL ENVIRON FRONTIERS IN ECOLOGY AND THE ENVIRONMENT GLOBAL CHANGE BIOL GLOBAL CHANGE BIOLOGYGLOBAL ECOL BIOGEOGR GLOBAL ECOLOGY AND BIOGEOGRAPHYISME J ISME JournalATMOS ENVIRON ATMOSPHERIC ENVIRONMENTCHEMOSPHERE CHEMOSPHEREENVIRON SCI TECHNOL ENVIRONMENTAL SCIENCE & TECHNOLOGYWATER RES WATER RESEARCHADV AGRON ADVANCES IN AGRONOMYAGR FOREST METEOROL AGRICULTURAL AND FOREST METEOROLOGYATLA-ALTERN LAB ANIM ATLA-ALTERNATIVES TO LABORATORY ANIMALSEUR J SOIL SCI EUROPEAN JOURNAL OF SOIL SCIENCEFISH FISH FISH AND FISHERIESFISH OCEANOGR FISHERIES OCEANOGRAPHYFISH SHELLFISH IMMUN FISH & SHELLFISH IMMUNOLOGYFOOD BIOPROCESS TECH Food and Bioprocess TechnologyGEODERMA GEODERMAILAR J ILAR JOURNALJ AGR FOOD CHEM JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRYJ ANIM SCI JOURNAL OF ANIMAL SCIENCEJ DAIRY SCI JOURNAL OF DAIRY SCIENCEMOL BREEDING MOLECULAR BREEDINGREV FISH BIOL FISHER REVIEWS IN FISH BIOLOGY AND FISHERIESSOIL BIOL BIOCHEM SOIL BIOLOGY & BIOCHEMISTRYSOIL SCI SOC AM J SOIL SCIENCE SOCIETY OF AMERICA JOURNALTREE PHYSIOL TREE PHYSIOLOGYVET MICROBIOL VETERINARY MICROBIOLOGYVET RES VETERINARY RESEARCHAQUACULTURE AQUACULTURECAN J FISH AQUAT SCI CANADIAN JOURNAL OF FISHERIES AND AQUATIC SCIENC FOREST ECOL MANAG FOREST ECOLOGY AND MANAGEMENTJAVMA-J AM VET MED A JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL PLANT SOIL PLANT AND SOILAM J BIOETHICS AMERICAN JOURNAL OF BIOETHICSECONOMETRICA ECONOMETRICAJ ECONOMETRICS JOURNAL OF ECONOMETRICSAM J HUM GENET AMERICAN JOURNAL OF HUMAN GENETICSANNU REV BIOCHEM ANNUAL REVIEW OF BIOCHEMISTRYANNU REV BIOPH BIOM ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STR ANNU REV BIOPHYS Annual Review of BiophysicsANNU REV CELL DEV BI ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY ANNU REV ECOL EVOL S ANNUAL REVIEW OF ECOLOGY EVOLUTION AND SYSTEMATI ANNU REV ENTOMOL ANNUAL REVIEW OF ENTOMOLOGYANNU REV GENET ANNUAL REVIEW OF GENETICSANNU REV GENOM HUM G ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS ANNU REV MICROBIOL ANNUAL REVIEW OF MICROBIOLOGYANNU REV PHYTOPATHOL ANNUAL REVIEW OF PHYTOPATHOLOGYANNU REV PLANT BIOL ANNUAL REVIEW OF PLANT BIOLOGYCELL CELLCELL HOST MICROBE Cell Host & MicrobeCELL METAB Cell MetabolismCELL STEM CELL Cell Stem CellCRIT REV BIOCHEM MOL CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR B CURR BIOL CURRENT BIOLOGYCURR OPIN CELL BIOL CURRENT OPINION IN CELL BIOLOGYCURR OPIN GENET DEV CURRENT OPINION IN GENETICS & DEVELOPMENTCURR OPIN PLANT BIOL CURRENT OPINION IN PLANT BIOLOGYCURR OPIN STRUC BIOL CURRENT OPINION IN STRUCTURAL BIOLOGYDEV CELL DEVELOPMENTAL CELLGENE DEV GENES & DEVELOPMENTGENOME RES GENOME RESEARCHJ CELL BIOL JOURNAL OF CELL BIOLOGYMICROBIOL MOL BIOL R MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWSMOL CELL MOLECULAR CELLMOL SYST BIOL Molecular Systems BiologyNAT CELL BIOL NATURE CELL BIOLOGYNAT CHEM BIOL Nature Chemical BiologyNAT GENET NATURE GENETICSNAT METHODS NATURE METHODSNAT REV 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Disease ANNU REV PHARMACOL ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY ANNU REV PHYSIOL ANNUAL REVIEW OF PHYSIOLOGYANNU REV PSYCHOL ANNUAL REVIEW OF PSYCHOLOGYANNU REV PUBL HEALTH ANNUAL REVIEW OF PUBLIC HEALTHARCH GEN PSYCHIAT ARCHIVES OF GENERAL PSYCHIATRYARCH INTERN MED ARCHIVES OF INTERNAL MEDICINEARTERIOSCL THROM VAS ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY ARTHRITIS RHEUM-US ARTHRITIS AND RHEUMATISMBBA-REV CANCER BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER BEHAV BRAIN SCI BEHAVIORAL AND BRAIN SCIENCESBIOL PSYCHIAT BIOLOGICAL PSYCHIATRYBLOOD BLOODBLOOD REV BLOOD REVIEWSBRAIN BRAINBRAIN RES REV BRAIN RESEARCH REVIEWSBRIT MED J BRITISH MEDICAL JOURNALCA-CANCER J CLIN CA-A CANCER JOURNAL FOR CLINICIANSCAN MED ASSOC J CANADIAN MEDICAL ASSOCIATION JOURNALCANCER CELL CANCER CELLCANCER METAST REV CANCER AND METASTASIS REVIEWSCANCER RES CANCER RESEARCHCEREB CORTEX CEREBRAL CORTEXCIRC RES CIRCULATION RESEARCHCIRCULATION CIRCULATIONCLIN CANCER RES CLINICAL CANCER RESEARCHCLIN INFECT DIS CLINICAL INFECTIOUS DISEASESCLIN MICROBIOL REV CLINICAL MICROBIOLOGY REVIEWSCLIN PHARMACOL THER CLINICAL PHARMACOLOGY & THERAPEUTICSCRIT CARE MED CRITICAL CARE MEDICINECURR OPIN IMMUNOL CURRENT OPINION IN IMMUNOLOGYCURR OPIN LIPIDOL CURRENT OPINION IN LIPIDOLOGYCURR OPIN NEUROBIOL CURRENT OPINION IN NEUROBIOLOGYCURR OPIN PHARMACOL CURRENT OPINION IN PHARMACOLOGYDIABETES DIABETESDIABETES CARE DIABETES CAREDIABETOLOGIA DIABETOLOGIADRUG DISCOV TODAY DRUG DISCOVERY TODAYDRUG RESIST UPDATE DRUG RESISTANCE UPDATESEMERG INFECT DIS EMERGING INFECTIOUS DISEASESENDOCR REV ENDOCRINE REVIEWSEPIDEMIOL REV EPIDEMIOLOGIC REVIEWSEUR HEART J EUROPEAN HEART JOURNALEUR UROL EUROPEAN UROLOGYFRONT NEUROENDOCRIN FRONTIERS IN NEUROENDOCRINOLOGY GASTROENTEROLOGY GASTROENTEROLOGYGASTROINTEST ENDOSC GASTROINTESTINAL ENDOSCOPYGUT GUTHEPATOLOGY HEPATOLOGYHUM MUTAT HUMAN MUTATIONHUM REPROD UPDATE HUMAN REPRODUCTION UPDATEHYPERTENSION HYPERTENSIONIMMUNITY IMMUNITYIMMUNOL REV IMMUNOLOGICAL REVIEWSJ ALLERGY CLIN IMMUN JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGYJ AM COLL CARDIOL JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGYJ AM SOC NEPHROL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGYJ AUTOIMMUN JOURNAL OF AUTOIMMUNITYJ BONE MINER RES JOURNAL OF BONE AND MINERAL RESEARCHJ CLIN INVEST JOURNAL OF CLINICAL INVESTIGATIONJ CLIN ONCOL JOURNAL OF CLINICAL ONCOLOGYJ EXP MED JOURNAL OF EXPERIMENTAL MEDICINEJ HEPATOL JOURNAL OF HEPATOLOGYJ NATL CANCER I JOURNAL OF THE NATIONAL CANCER INSTITUTEJ NEUROSCI JOURNAL OF NEUROSCIENCEJ NUCL MED JOURNAL OF NUCLEAR MEDICINEJAMA-J AM MED ASSOC JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LANCET LANCETLANCET INFECT DIS LANCET INFECTIOUS DISEASESLANCET NEUROL LANCET NEUROLOGYLANCET ONCOL LANCET ONCOLOGYLEUKEMIA LEUKEMIAMED RES REV MEDICINAL RESEARCH REVIEWSMOL ASPECTS MED MOLECULAR ASPECTS OF MEDICINEMOL PSYCHIATR MOLECULAR PSYCHIATRYNAT CLIN PRACT ONCOL Nature Clinical Practice OncologyNAT IMMUNOL NATURE IMMUNOLOGYNAT MED NATURE MEDICINENAT NEUROSCI NATURE NEUROSCIENCENAT REV CANCER NATURE REVIEWS CANCERNAT REV DRUG DISCOV NATURE REVIEWS DRUG DISCOVERYNAT REV IMMUNOL NATURE REVIEWS IMMUNOLOGYNAT REV NEUROSCI NATURE REVIEWS NEUROSCIENCENEUROLOGY NEUROLOGYNEURON NEURONNEUROPSYCHOPHARMACOL NEUROPSYCHOPHARMACOLOGYNEUROSCI BIOBEHAV R NEUROSCIENCE AND BIOBEHAVIORAL REVIEWSNEW ENGL J MED NEW ENGLAND JOURNAL OF MEDICINEOBES REV Obesity ReviewsONCOGENE ONCOGENEPHARMACOL REV PHARMACOLOGICAL REVIEWSPHARMACOL THERAPEUT PHARMACOLOGY & THERAPEUTICSPHYSIOL REV PHYSIOLOGICAL REVIEWSPHYSIOLOGY PHYSIOLOGYPLOS MED PLOS MEDICINEPROG NEUROBIOL PROGRESS IN NEUROBIOLOGYPROG RETIN EYE RES PROGRESS IN RETINAL AND EYE RESEARCHPSYCHOL BULL PSYCHOLOGICAL BULLETINPSYCHOL REV PSYCHOLOGICAL REVIEWREV MED VIROL REVIEWS IN MEDICAL VIROLOGYSCHIZOPHRENIA BULL SCHIZOPHRENIA BULLETINSEMIN CANCER BIOL SEMINARS IN CANCER BIOLOGYSEMIN IMMUNOL SEMINARS IN IMMUNOLOGYSTEM CELLS STEM CELLSSTROKE STROKETHORAX THORAXTRENDS COGN SCI TRENDS IN COGNITIVE SCIENCESTRENDS ENDOCRIN MET TRENDS IN ENDOCRINOLOGY AND METABOLISMTRENDS IMMUNOL TRENDS IN IMMUNOLOGYTRENDS MOL MED TRENDS IN MOLECULAR MEDICINETRENDS NEUROSCI TRENDS IN NEUROSCIENCESTRENDS PHARMACOL SCI TRENDS IN PHARMACOLOGICAL SCIENCESWHO TECH REP SER WHO TECHNICAL REPORT SERIESAM J CARDIOL AMERICAN JOURNAL OF CARDIOLOGYAM J EPIDEMIOL AMERICAN JOURNAL OF EPIDEMIOLOGYAM J PATHOL AMERICAN JOURNAL OF PATHOLOGYAM J PHYSIOL-HEART C AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULA ANTIMICROB AGENTS CH ANTIMICROBIAL AGENTS AND CHEMOTHERAPYBRIT J CANCER BRITISH JOURNAL OF CANCERCANCER-AM CANCER SOC CANCERCHEST CHESTCNS NEUROL DISORD-DR CNS & Neurological Disorders-Drug Targets ENDOCRINOLOGY ENDOCRINOLOGYEUR J NEUROSCI EUROPEAN JOURNAL OF NEUROSCIENCEFREE RADICAL BIO MED FREE RADICAL BIOLOGY AND MEDICINEINFECT IMMUN INFECTION AND IMMUNITYINT J CANCER INTERNATIONAL JOURNAL OF CANCERINT J RADIAT ONCOL INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOL INVEST OPHTH VIS SCI INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCEJ APPL PHYSIOL JOURNAL OF APPLIED PHYSIOLOGYJ CLIN ENDOCR METAB JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM J CLIN MICROBIOL JOURNAL OF CLINICAL MICROBIOLOGYJ COMP NEUROL JOURNAL OF COMPARATIVE NEUROLOGYJ IMMUNOL JOURNAL OF IMMUNOLOGYJ INFECT DIS JOURNAL OF INFECTIOUS DISEASESJ MED CHEM JOURNAL OF MEDICINAL CHEMISTRYJ NEUROCHEM JOURNAL OF NEUROCHEMISTRYJ NEUROPHYSIOL JOURNAL OF NEUROPHYSIOLOGYJ NUTR JOURNAL OF NUTRITIONJ PHARMACOL EXP THER JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPE J PHYSIOL-LONDON JOURNAL OF PHYSIOLOGY-LONDONJ UROLOGY JOURNAL OF UROLOGYJ VIROL JOURNAL OF VIROLOGYKIDNEY INT KIDNEY INTERNATIONALNEUROIMAGE NEUROIMAGENEUROSCIENCE NEUROSCIENCEPEDIATRICS PEDIATRICSRADIOLOGY RADIOLOGYTRANSPLANTATION TRANSPLANTATIONVIROLOGY VIROLOGYNATURE NATUREP NATL ACAD SCI USA PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES SCIENCE SCIENCEANN NY ACAD SCI ANNALS OF THE NEW YORK ACADEMY OF SCIENCESISSN大类名称复分大类分区是否top期刊2009年影响因子1680-7316地学1Y 4.881 0003-0007地学1Y 6.123 0930-7575地学1Y 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尼洛替尼化学结构式
尼洛替尼化学结构式
尼洛替尼（Nilotinib）是一种用于治疗慢性髓细胞白血病（CML）的药物。
它属于一类被称为酪氨酸激酶抑制剂的药物，通过抑制异常的酪氨酸激酶活性来阻止白血病细胞的生长和分裂。
尼洛替尼的化学结构式如下：
C₂₂H₂₈ClN₇O₄S
这种化合物由碳、氢、氯、氮、氧和硫等元素组成。
在化学结构中，氢原子用H表示，碳原子用C表示，氯原子用Cl表示，氮原子用N表示，氧原子用O表示，硫原子用S表示。
尼洛替尼的化学结构式展示了其分子的组成和排列方式。
它由一个环状的苯乙酸酰胺基团和一个咪唑基团组成。
苯乙酸酰胺基团包含一个苯环和一个乙酸酰胺基团，而咪唑基团则包含一个咪唑环和一个胺基团。
尼洛替尼的化学结构式向我们展示了这种药物的分子结构特征。
通过理解其结构，我们可以更好地理解尼洛替尼的作用机制和药效。
尼洛替尼的独特结构使其能够与特定的酪氨酸激酶结合，并抑制其活性。
这种抑制作用可以阻止白血病细胞的生长和分裂，从而抑制疾病的发展。
尼洛替尼的化学结构式让我们更好地了解了这种药物的本质，它是
现代医学中的一项重要成就。
通过研究和理解药物的化学结构，我们可以为患者提供更好的治疗方案，帮助他们战胜疾病，重返健康。
恩曲替尼化学式-概述说明以及解释
恩曲替尼化学式-概述说明以及解释1.引言1.1 概述概述恩曲替尼（英文名称：Entrectinib）是一种靶向抗癌药物，属于酪氨酸激酶抑制剂。
它通过抑制肿瘤细胞中的激酶信号通路，发挥抗肿瘤的作用。
恩曲替尼被广泛应用于非小细胞肺癌、神经母细胞瘤和其他肿瘤的治疗。
该药物的化学性质使其具备出色的抗肿瘤效果。
恩曲替尼的分子式为C31H34Cl2N5O3，分子量为602.54克/摩尔。
其分子结构复杂，由多个不同原子组成的编织网状结构构成。
这种特殊的结构赋予了恩曲替尼优异的特性，包括其强大的抑制肿瘤生长能力和独特的靶向治疗机制。
除了化学性质外，恩曲替尼还具有一系列独特的物理性质。
该药物为白色或类白色结晶粉末，具有极高的纯度要求。
其熔点为210-215，在这个温度范围内可以保持稳定。
此外，恩曲替尼在常温下可溶于一些有机溶剂，如二氯甲烷和二甲基亚砜，但不溶于水。
在药理作用方面，恩曲替尼主要表现出针对肿瘤细胞的抗增殖和抗转移能力。
它通过干扰肿瘤细胞的激酶信号通路，阻止肿瘤细胞的分裂和生长。
此外，恩曲替尼还具有特异性靶向治疗作用，能够选择性地抑制特定的激酶，从而实现精确的治疗效果。
然而，恩曲替尼也存在一些副作用，如恶心、呕吐、疲劳和食欲不振等，这些副作用需在使用时留意并及时处理。
综上所述，恩曲替尼作为一种靶向抗肿瘤药物，具有复杂的化学性质、独特的物理性质以及较广泛的药理作用。
进一步的研究和应用将有助于更好地发掘恩曲替尼的潜力，为肿瘤治疗提供新的突破和可能性。
1.2 文章结构文章结构部分的内容如下：文章结构部分主要介绍了整篇文章的组织结构和内容安排。
本文的目录分为引言、正文和结论三个部分。
引言部分主要是对整篇文章的背景和目的进行概述，并对恩曲替尼的化学式进行引入。
接着，文章结构部分将详细介绍恩曲替尼的化学性质、物理性质和药理作用。
最后，结论部分将对恩曲替尼的化学性质、物理性质和药理作用进行总结。
在正文部分，恩曲替尼的化学性质将包括分子式、分子量和结构式的介绍。
生物合成青蒿酸课件
7
生物合成青蒿酸
菌株改造：
Y337 (原始菌株， PMET3-ERG9 )
导入表达CYP71AV1 和CPR1 基因的高 拷贝质粒
14
结果
添加10%的IPM，使得所有菌株的生存能力显著加强。同时，对Y285 、Y301、Y657和 Y692菌株(缺乏ALDH1和ADH1基因)而言，添加IPM会导致中间产物的析出。而对有 ALDH1和ADH1基因的菌株，添加IPM会提高青蒿酸的产量
15
化学途径
1.the reduction of the D11(13) double bond. 2. the esterification of the carboxylic acid. 3. an ‘ene-type’ reaction of the C4 –C5 double bond with singlet oxygen. 4. the allylic hydroperoxide undergoes an acid-catalysed Hock fragmentation and rearrangement to afford a ringopened ketoaldehyde enol
12
添加IMP
表达ALDH1基因的菌株以胞外晶体沉淀的形式生产青蒿 酸，沉淀在初期发酵时便能观察到，这对使得多相发酵样 品中产品的精确测量变得复杂。为了克服由青蒿酸结晶沉 淀带来的困难，我们利用萃取发酵溶解沉淀的现象，在十 四酸异丙酯(IMP)环境中培养菌体。
维A酸脂质体乳膏的制备与质量评价
广东药科大学学报Journal of Guangdong Pharmaceutical University Nov,2023,39(6)维A酸脂质体乳膏的制备与质量评价郑燕燕，颜利，郝吉福，何玉静［山东第一医科大学（山东省医学科学院）药学院/先进药物递送系统全国重点实验室，山东济南271000］摘要：目的制备维A酸脂质体乳膏并对其进行质量评价，为维A酸的应用提供新思路。
方法采用乙醇注入法制备维A酸脂质体，以包封率和载药量为综合评价指标筛选最佳制备工艺。
采用乳化法制备维A酸脂质体乳膏，采用Franz扩散池对维A酸脂质体乳膏和普通维A酸乳膏进行体外经皮渗透速率的测定。
结果维A酸脂质体的最佳制备工艺为：磷脂质量浓度为16mg/mL，磷脂与胆固醇质量比为5∶1，药脂比为1∶40，水浴温度为60℃；所得脂质体包封率为89.44%，载药量为2.19%。
维A酸脂质体乳膏渗透速率为（0.6558±0.0319）（μg·h）/cm2，高于普通维A酸乳膏[（0.4427±0.0345）（μg·h）/cm2]；24h累积渗透量为（17.18±1.96）μg/cm2，高于普通维A酸乳膏[（8.9646±0.3942）μg/cm2]。
结论乙醇注入法制备维A酸脂质体的工艺简单，包封率高；相较于普通维A酸乳膏，维A酸脂质体乳膏可以提高维A酸的经皮渗透速率和累积渗透量。
关键词：维A酸；脂质体乳膏；包封率；载药量；经皮渗透速率中图分类号：R944.6文献标识码：A文章编号：2096-3653（2023）06-0092-06DOI:10.16809/ki.2096-3653.2023101103Preparation and quality evaluation of retinoic acid liposome creamZHENG Yanyan,YAN Li,HAO Jifu,HE Yujing*[Shandong First Medical University(Shandong Academy of Medical Sciences)&School of Pharmaceutical Science/National Key Laboratory of Advanced Drug Delivery Systems,Jinan271000,China]*Corresponding author Email:******************Abstract:Objective To prepare retinoic acid liposome cream and evaluate its quality,which will provide new ideas for the application of retinoic acid.Methods Retinoic acid liposomes were prepared by ethanol injection method,and the optimal preparation technology was screened with the encapsulation rate and drug loading as comprehensive evaluation indexes.The retinoic acid liposome cream was prepared by emulsion method.Percutaneous penetration rate of retinoic acid liposome cream and retinoic acid cream was measured by Franz diffusion cell.Results The best preparation technology was as follows:the concentration of phospholipid was 16mg/mL,the ratio of phospholipid to cholesterol was5∶1,the ratio of drug to lipid was1∶40,and the bath temperature was60℃.The encapsulation rate of liposomes reached89.44%,the drug loading capacity of liposomes reached2.19%.The penetration rate of retinoic acid liposome cream was(0.6558±0.0391)(μg·h)/cm2, which was higher than that of retinoic acid cream by(0.4427±0.0345)(μg·h)/cm2,and the cumulativewhich was higher than that of permeability of retinoic acid liposome cream in24hours was(17.18±1.96)μg/cm2,retinoic acid cream by(8.9646±0.3942)μg/cm2.Conclusion The ethanol injection method for preparing retinoic acid liposomes has a simple process and high encapsulation efficiency.The penetration rate and the accumulated permeability of retinoic acid liposome cream are higher than that of retinoic acid cream.Key words:retinoic acid;liposome cream;encapsulation rate;drug loading capacity;penetration rate收稿日期：2023-10-11基金项目：国家自然科学基金-青年项目（82003677）；山东省自然科学基金-青年项目（ZR2020QH352）；山东第一医科大学本科生研究计划（SRTP）暨大学生创新创业训练计划项目（2022104391584）作者简介：郑燕燕（2000－），女，2023级硕士研究生，Email:131****************通信作者：何玉静（1991－），女，从事药剂学及药物新剂型研究与开发，Email:******************。
伊布替尼 平面结构 溶解度
伊布替尼平面结构溶解度
【原创实用版】
目录
1.伊布替尼的简介
2.伊布替尼的平面结构
3.伊布替尼的溶解度
4.伊布替尼的应用领域
正文
伊布替尼是一种用于治疗慢性髓系白血病和费城染色体阳性急性淋巴细胞性白血病的药物，其化学名为“4-[(4-甲基 -1-哌嗪) 甲
基]-N-[4-[(3-甲基 -2-氧代 -5-咪唑啉 -4-基) 甲基]-2-甲基苯胺]-3-甲基 -2-氧代 -5-咪唑啉 -4-羧酸”。
它的平面结构由一个哌嗪环、一个咪唑啉环和一个苯胺环组成，这三个环通过共价键连接在一起，构成了伊布替尼的基本骨架。
伊布替尼的溶解度是指其在水中的溶解程度。
一般来说，伊布替尼在水中的溶解度较低，但在某些有机溶剂中的溶解度较高。
这一特性决定了伊布替尼在制备和应用过程中需要特别注意溶解度的问题，以保证药物的有效成分能够被充分吸收和利用。
伊布替尼的应用领域非常广泛，除了上述提到的治疗慢性髓系白血病和费城染色体阳性急性淋巴细胞性白血病外，还用于治疗多种实体瘤，如肺癌、胃癌等。
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重组人促红素联合左卡尼汀治疗方案在血液透析肾性贫血患者中的疗效分析
药物与临床China &Foreign Medical Treatment 中外医疗重组人促红素联合左卡尼汀治疗方案在血液透析肾性贫血患者中的疗效分析劳敏琴，陈思念，何颖梅佛山市三水区人民医院肾脏风湿免疫科，广东佛山 528100［摘要］ 目的 探究血液透析肾性贫血患者采用重组人促红素联合左卡尼汀治疗方案的疗效。
方法 通过计算机随机选取2019年8月—2021年8月在佛山市三水区人民医院开展常规透析期间伴有贫血的慢性肾功能衰竭患者100例为研究对象，随机分为对照组和研究组，各50例。
对照组给予重组人促红细胞生成素注射液，研究组给予左卡尼汀联合重组人促红细胞生成素注射液。
比较两组患者用药后的临床疗效、贫血相关生化指标和不良反应发生率。
结果 研究组的治疗总有效率为96.00%，高于对照组的78.00%，差异有统计学意义（χ2=7.162，P <0.05）。
治疗后，两组患者的平均红细胞血红蛋白浓度、平均红细胞血红蛋白含量、平均红细胞血红蛋白体积、血清铁蛋白水平均高于治疗前，且研究组高于对照组，差异有统计学意义（P <0.05）。
结论 在定期透析的慢性肾功能衰竭合并贫血患者中，左卡尼汀和重组人促红细胞生成素注射液的联合应用安全有效，可以获得更好的治疗效果，提高贫血相关生化标志物水平，并且不良反应发生率低。
［关键词］ 肾性贫血；重组人促红素；尿毒症；左卡尼汀；维持性血液透析［中图分类号］ R692.5 ［文献标识码］ A ［文章编号］ 1674-0742（2023）03(c)-0107-04Therapeutic Effect of Recombinant Human Erythropoietin Combined with L-carnitine in Patients with Hemodialysis Renal AnemiaLAO Minqin, CHEN Sinian, HE YingmeiDepartment of Renal Rheumatology, Sanshui District People's Hospital, Foshan, Guangdong Province, 528100 China [Abstract] Objective To explore the therapeutic effect of recombinant human erythropoietin combined with L-carnitine in patients with renal anemia after hemodialysis. Methods A total of 100 patients with chronic renal failure with anemia during routine dialysis in Sanshui District People's Hospital of Foshan City from August 2019 to August 2021 were randomly selected as the study objects by computer, and randomly divided into control group and study group, with 50 cases in each group. The control group was given recombinant human erythropoietin injection, and the study group was given L-carnitine combined with recombinant human erythropoietin injection. The clinical effi⁃cacy, anemic related biochemical indexes and incidence of adverse reactions were compared between the two groups. Results The total effective rate in the study group was 96.00%, which were higher than that of 78.00% in the controlgroup, the difference was statistically significant (χ2=7.162, P <0.05). After treatment, the mean RBC hemoglobin con⁃centration, mean RBC hemoglobin content, mean RBC hemoglobin volume and serum ferritin level in two groups were higher than before treatment, and the study group was higher than the control group, the difference was statistically sig⁃nificant (P <0.05). Conclusion In patients with chronic renal failure and anemia on regular dialysis, the combination ofL-carnitine and recombinant human erythropoietin injection is safe and effective, resulting in better therapeutic out⁃comes, improved levels of anemia-related biochemical markers, and a low incidence of adverse reactions.[Key words] Renal anemia; Recombinant human erythropoietin; Uremia; L-carnitine; Maintenance hemodialysis DOI ：10.16662/ki.1674-0742.2023.09.107[作者简介] 劳敏琴（1987-），女，本科，主治医生，研究方向为血液净化。
重组人锰超氧化物歧化酶的抗肿瘤作用研究
重组人锰超氧化物歧化酶的抗肿瘤作用研究陈车生1，庞怀宇2，李素霞2，袁勤生2*1上海富海科申药业有限公司，2华东理工大学生物工程学院，上海200237摘要：论文主要研究了rhMnSOD的体内抗肿瘤作用、对荷瘤小鼠的体内单独使用的抗肿瘤作用、与化疗药物合用的抗肿瘤作用以及抗肿瘤作用机制探讨。
关键词：重组人锰超氧化物歧化酶，抗肿瘤，化疗药物，荷瘤小鼠前言MnSOD是哺乳动物体内的一线抗氧化酶，其在体内的生理代谢过程中不仅是一个氧化还原调节剂，其还是一个肿瘤抑制子。
已经在黑色素瘤、乳腺癌等多个肿瘤模型中发现，通过cDNA转染使得肿瘤细胞中MnSOD过表达，肿瘤细胞的恶性表型发生逆转，肿瘤细胞分化增加。
而rhMnSOD的作用机制可能与其他抗肿瘤药物作用有所不同，因为到目前为止，没有研究证据证明MnSOD具有有细胞毒作用，因此其抗肿瘤作用应该是间接的。
我们对此进行了研究。
最近有报道给予小鼠服用rh MnSOD后产生积极的抗氧化作用，并且增加小鼠的体液免疫能力。
因此，很可能给予rh MnSOD治疗能够保护小鼠的免疫系统免受自由基的氧化损伤，同时能够促进T淋巴细胞募集进入肿瘤组织杀死肿瘤细胞，从而增强抗肿瘤免疫应答。
对于rhMnSOD的抗肿瘤作用还需要在更多种类的肿瘤中进行验证，也需要检测其与更多的化疗药物的协同作用，并对其作用机制进行更为深入的研究。
根据目前已经发表的结果我们可以预期rhMnSOD和ADR合用能够降低ADR的心脏毒性等副反应，因此，作为抗肿瘤的辅助治疗药物，rhMnSOD具有很大的开发潜力。
1 材料RPMI-1640培养基，美国GIBCO公司；小牛血清，杭州四季青物工程公司；MTT，美国Sigma公司；PI/RNase Staining Buffer ，美国Becton Dickinson公司；AnnexinV-EGFP双染试剂盒，南京凯基生物科技发展有限公司；注射用盐酸阿霉素，10 mg/瓶，批号：060705浙江海正药业股份有限公司；注射用环磷酰胺，200 mg/瓶，批号：06060121江苏恒瑞医药股份有限公司；羊抗人CD4多克隆抗体、兔抗人CD8多克隆抗体，羊抗人肌动蛋白多克隆抗体，美国Santa Cruz 公司；IRDyeTM800结合二抗，美国Rockland Inc；SP试剂盒、DAB显色剂，北京中杉金桥公司。
利用Mitsunobu反应合成川芎嗪衍生物
利用Mitsunobu反应合成川芎嗪衍生物王慧颖;孙平华;陈卫民【摘要】以川芎嗪为起始原料,利用Mitsunobu反应合成了三个3,5,6.三甲基吡嗪.2-基-甲氧基苯甲醛衍生物,收率87%～92%.其结构经1H NMR,13C NMR和ESI-MS表征.%Three tetramethylpyrazine derivatives in yields of 87％～ 92％were synthesized by Mitsunobu reaction from tetramethylpyrazine. The structures were characterized by 1H NMR, 13C NMR and ESI-MS.【期刊名称】《合成化学》【年(卷),期】2011(019)003【总页数】3页(P430-432)【关键词】川芎嗪;Mitsunobu反应;合成【作者】王慧颖;孙平华;陈卫民【作者单位】暨南大学药学院,广东,广州,510632;暨南大学药学院,广东,广州,510632;暨南大学药学院,广东,广州,510632【正文语种】中文【中图分类】O626;R914.5川芎嗪(1)是从川芎中分离出的生物碱单体，具有抑制血小板聚集、抗血栓形成、抗自由基等作用。
临床上广泛用于治疗缺血性心、脑血管疾病，冠心病及呼吸系统疾病[1，2]。
研究发现，1的吡嗪环是决定其药理作用的重要结构部分，即药效基团，而1的甲基很容易被氧化代谢，生成极性和水溶性都较大的代谢产物迅速排出体外，存在代谢快、半衰期短、生物利用度低等缺点[2～4]。
因此，现在多以1为先导化合物进行结构修饰，以阻滞或延缓其甲基的氧化代谢，从而延长作用时间、相对增加药效。
对于1的修饰主要有以下方法：利用H2O2氧化1得到对应的单氮氧化物；再与乙酸酐发生重排反应生成2-乙酰氧基甲基-3,5,6-三甲基吡嗪(M1)； M1在碱性条件下水解制得2-羟甲基-3,5,6-三甲基吡嗪(2)；继而进行进一步的结构修饰[5～8]。
欧盟对草莓中的农残限量要求
0,02*
0,02*
0,02* 0,05*
Cypermethrin (cypermethrin including other mixtures of constituent isomers (sum of isomers)) (F) Cyproconazole (F) Cyprodinil (F) (R) Cyromazine Dalapon Daminozide (sum of daminozide and 1,1-dimethyl-hydrazine, expressed as daminozide) Dazomet (Methylisothiocyanate resulting from the use of dazomet and metam) DDT (sum of p,p´-DDT, o,p´-DDT, p-p´-DDE and p,p´-TDE (DDD) expressed as DDT) (F) Deltamethrin (cis-deltamethrin) (F) Desmedipham Diallate Diazinon (F) Dicamba Dichlobenil Dichlorprop: sum of dichlorprop (including dichlorprop-P) and its conjugates, expressed as dichlorprop Dichlorvos
1 0,01* 0,05* 0,01* 0,02 0,01* 0,01* 0,02* 0,1* 0,05* 0,02* 0,05
5 0,05* 0,05* 0,05* 0,2 0,5 0,05* 0,01* 0,01* 0,05* 0,01* 0,05*
0,5
0,02* 2
叶绿素三酸对小鼠移植瘤S180抑瘤作用的探讨
叶绿素三酸对小鼠移植瘤S180抑瘤作用的探讨
刘宁娜;苏明
【期刊名称】《陕西医学杂志》
【年(卷),期】1993(022)007
【摘要】应用新型光敏剂叶绿素三酸(Chlorine6)加He—Ne激光的体外照射,对小鼠S_(180)移植瘤抑瘤作用的研究结果表明:实验组与对照组相比,给药照光组的抑瘤率为72%(P<0.05),有显著的抗肿瘤效应。
单给药组抑瘤率41%,单照光组抑瘤率42%,说明单给叶绿素三酸或单纯He-Ne 激光照射对S_(180)移植瘤均有一定的抑制作用,但P<0.05,与对照组间无显著性差异。
因此,只有在给予叶绿素三酸的同时进行光激激活才能达到有效的治疗结果。
【总页数】2页(P440-441)
【作者】刘宁娜;苏明
【作者单位】不详;不详
【正文语种】中文
【中图分类】R730.59
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2.乳鼠心肌裂解液对S180小鼠移植瘤抑瘤作用的实验研究 [J], 蒋晓睿;吴敬波;王莹
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酶解-柱前衍生UPLC_法检测特医食品中天冬酰胺及谷氨酰胺
引用格式：范志颖, 王奇, 吴益淳, 等. 酶解-柱前衍生UPLC 法检测特医食品中天冬酰胺及谷氨酰胺[J]. 中国测试，2023, 49(11):127-131. FAN Zhiying, WANG Qi, WU Yichun, et al. Enzymatic hydrolysis pre-column derivatisation UPLC method for the detection of asparagine and glutamine in FSMP[J]. China Measurement & Test, 2023, 49(11): 127-131. DOI : 10.11857/j.issn.1674-5124.2023040135酶解-柱前衍生UPLC 法检测特医食品中天冬酰胺及谷氨酰胺范志颖1,2， 王 奇2， 吴益淳2， 罗 敏2， 肖伟敏2， 包跃超1， 蓝 雄2，陈佳平2， 杨国武2， 杨 燕3(1. 内蒙古科技大学包头医学院，内蒙古 包头 014040; 2. 深圳市计量质量检测研究院，广东 深圳 518109;3. 中山大学深圳校区公共卫生学院（深圳），广东 深圳 518107)摘 要: 建立酶水解-丹磺酰氯柱前衍生高效液相色谱法检测特殊医学用途配方食品（FSMP ）中天冬酰胺（Asn ）和谷氨酰胺（Gln ）的方法。
样品经灰色链霉菌蛋白酶（Pronase E ）酶解后，取上清液与Dns-Cl 进行柱前衍生，衍生化产物经Agilent Zorbax SB-C18色谱柱（250 mm×4. 6 mm ，5 μm ）分离，以10 mmol/L 磷酸氢二钠溶液(pH 6.5)和甲醇作为流动相进行梯度洗脱，外标法定量。
结果表明，两种氨基酸在0.500~50.0 μg/mL 浓度范围内线性良好（R ≥0.999），回收率为95.3%~105%，RSD 为0.95%~3.22%。