全文获取类型
收费全文 | 1655篇 |
免费 | 168篇 |
国内免费 | 435篇 |
出版年
2023年 | 25篇 |
2022年 | 63篇 |
2021年 | 78篇 |
2020年 | 59篇 |
2019年 | 58篇 |
2018年 | 65篇 |
2017年 | 42篇 |
2016年 | 37篇 |
2015年 | 67篇 |
2014年 | 87篇 |
2013年 | 119篇 |
2012年 | 135篇 |
2011年 | 126篇 |
2010年 | 95篇 |
2009年 | 110篇 |
2008年 | 97篇 |
2007年 | 83篇 |
2006年 | 90篇 |
2005年 | 83篇 |
2004年 | 79篇 |
2003年 | 63篇 |
2002年 | 84篇 |
2001年 | 70篇 |
2000年 | 59篇 |
1999年 | 41篇 |
1998年 | 13篇 |
1997年 | 20篇 |
1996年 | 7篇 |
1995年 | 12篇 |
1994年 | 12篇 |
1993年 | 12篇 |
1992年 | 26篇 |
1991年 | 13篇 |
1990年 | 20篇 |
1989年 | 21篇 |
1988年 | 15篇 |
1987年 | 15篇 |
1986年 | 10篇 |
1985年 | 12篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 8篇 |
1980年 | 7篇 |
1979年 | 17篇 |
1975年 | 10篇 |
1973年 | 8篇 |
1972年 | 6篇 |
1971年 | 12篇 |
1970年 | 8篇 |
排序方式: 共有2258条查询结果,搜索用时 15 毫秒
101.
Siddiqui MI Kataria S Ahuja V Rao GS 《Indian journal of biochemistry & biophysics》2001,38(1-2):90-95
HIV-1 encodes an aspartic protease, an enzyme crucial to viral maturation and infectivity. It is responsible for the cleavage of various protein precursors into viral proteins. Inhibition of this enzyme prevents the formation of mature, infective viral particles and therefore, it is a potential target for therapeutic intervention following infection. Several drugs that inhibit the action of this enzyme have been discovered. These include peptidomimetic inhibitors such as ABT-538 and saquinavir, and structure based inhibitors such as indinavir and nelfinavir. Several of these have been tested in human clinical trials and have demonstrated significant reduction in viral load. However, most of them have been found to be of limited clinical utility because of their poor pharmacological properties and also because the viral protease becomes rapidly resistant to these drugs on account of mutations in the enzyme. One way to overcome these limitations is to design an inhibitor that interacts mainly with the conserved residues of HIV-1 protease. By a rational drug design approach based on the high resolution X-ray crystal structure of the HIV-1 protease with--MVT 101 (a substrate based inhibitor) and the specific design principles of peptides containing dehydro-Alanine (delta Ala) derived from our earlier studies, we have designed a tetrapeptide with the sequence: NH2-Thr-delta Ala-delta Ala-Gln-COOH. Energy minimization and molecular modelling of the interaction of the designed tetrapeptide with the inhibitor binding site indicate that the inhibitor is in an extended conformation and makes excessive contacts with the viral enzyme at the interface between the protein subunits. The designed inhibitor has 33% of its interaction with the conserved region of HIV-1 protease which is of the same order as that of MVT 101 with the enzyme. 相似文献
102.
Sultana R Fuchs R Schmickler H Schlegel K Budzikiewicz H Siddiqui BS Geoffrey V Meyer JM 《Zeitschrift für Naturforschung. C, Journal of biosciences》2000,55(11-12):857-865
From Pseudomonas sp. CFML 95-275 a pyoverdin was isolated with a cyclopeptidic substructure. It could be shown that this pyoverdin is identical with one obtained from Pseudomonas fluorescens BTP 7 for which a lactone structure had been deduced from the interpretation of a FAB spectrum. The elucidation of the correct structure of the pyoverdin is described. 相似文献
103.
Ford H Dai F Mu L Siddiqui MA Nicklaus MC Anderson L Marquez VE Barchi JJ 《Biochemistry》2000,39(10):2581-2592
Several recent X-ray crystal structures of adenosine deaminase (ADA) in complex with various adenosine surrogates have illustrated the preferred mode of substrate binding for this enzyme. To define more specific structural details of substrate preferences for binding and catalysis, we have studied the ADA binding efficiencies and deamination kinetics of several synthetic adenosine analogues in which the furanosyl ring is biased toward a particular conformation. NMR solution studies and pseudorotational analyses were used to ascertain the preferred furanose ring puckers (P, nu(MAX)) and rotamer distributions (chi and gamma) of the nucleoside analogues. It was shown that derivatives which are biased toward a "Northern" (3'-endo, N) sugar ring pucker were deaminated up to 65-fold faster and bound more tightly to the enzyme than those that preferred a "Southern" (2'-endo, S) conformation. This behavior, however, could be modulated by other structural factors. Similarly, purine riboside inhibitors of ADA that prefer the N hemisphere were more potent inhibitors than S analogues. These binding propensities were corroborated by detailed molecular modeling studies. Docking of both N- and S-type analogues into the ADA crystal structure coordinates showed that N-type substrates formed a stable complex with ADA, whereas for S-type substrates, it was necessary for the sugar pucker to adjust to a 3'-endo (N-type) conformation to remain in the ADA substrate binding site. These data outline the intricate structural details for optimum binding in the catalytic cleft of ADA. 相似文献
104.
A full length cDNA (1463 bp) encoding isocitrate lyase (EC 4.1.3.1) of Strongyloides stercoralis is described. The nucleotide sequence of this insert identified a cDNA coding for the isocitrate lyase. The conceptually translated amino acid sequence of the open reading frame for S. stercoralis isocitrate lyase encodes a 450 amino acid residue protein with an apparent molecular weight of 50 kDa and a predicted pl of 6.39. The sequence is 69% A/T, reflecting a characteristic A/T codon bias of S. stercoralis. The amino acid sequence of S. stercoralis isocitrate lyase is compared with bifunctional glyoxylate cycle protein of Caenorhabditis elegans and isocitrate lyases from Chlamydomonas reinhardtii and Myxococcus xanthus. The full length cDNA of S. stercoralis was expressed in pRSET vector and bacteriophage T7 promoter based expression system. S. stercoralis lyase recombinant protein, purified via immobilized metal affinity chromatography, showed a molecular mass of 50 kDa on polyacrylamide gels. The role of isocitrate lyase in the glyoxylate cycle and energy metabolism of S. stercoralis is also discussed. 相似文献
105.
Ahmed Jawaad Afzal Salim Ahmed Bokhari Waseem Ahmad Mohammad Hamid Rashid Mohammad Ibrahim Rajoka Khawar Sohail Siddiqui 《Biotechnology letters》2000,22(11):957-960
Two sensitive, high-resolution and exceedingly versatile methods for the detection of isoenzymes of polymer-degrading enzymes on high-resolution, alkaline, cold, in situ-native (HiRACIN)-PAGE and high-resolution in situ-inhibited, native (HiRISIN)-PAGE are described. Extracellular crude extracts containing xylanases and carboxymethylcellulases from Scopulariopsis sp. and glucoamylases from Aspergillus niger were subjected to non-denaturing PAGE containing substrates in the resolving gel. In case of HiRACIN-PAGE, the enzymes were prevented from degrading their respective substrates during run by carrying out electrophoresis at 4°C and the pH of running and resolving gel buffer systems were increased from 8.5 to 10.6. In case of HiRISIN-PAGE, adding competitive inhibitor of the enzyme, cellobiose, in the resolving gel prevents the degradation of polymer during the run. These techniques were successfully applied, for the first time, to visualize four, three and four sharp and distinct bands of xylanases, glucoamylases and CMCases, respectively. 相似文献
106.
本研究在初步实现水稻原生质体培养的程序化后,选用普通栽培稻P339和特种稻苏御糯选的原生质体为融合亲本,利用碘乙酸(IA)和罗丹明-6G(R-6G)这两个代谢互补抑制剂钝化处理亲本原生质体,确定了合适的抑制条件。P339用0.25mmol/L IA,苏御糯选用50μg/ml R-6G分别经30min钝化处理,通过PEG和高Ca~(2 )、高pH法诱导融合,异源融合体具有代谢互补效应,经培养得到愈伤组织17块,并进一步分化获得不同形态的再生植株12棵。移栽存活的再生植株成熟后可育,通过对这些植株的形态以及酯酶和过氧化物酶同工酶电泳的分析表明是融合后的体细胞杂种植株。 相似文献
107.
108.
磁性氧化铁纳米粒子因具有尺寸小、低毒性和超顺磁性等特点,已经引起了生物化工、医药工业领域的广泛关注。生物可降解高分子材料是生物医用高分子研究中最活跃的领域之一,已广泛用于外科手术缝合线,植入体材料及药物释放载体等。将Fe3O4和生物可降解高分子材料进行复合,可以扩大两者的应用范围,达到理想的治疗效果,并有望开创临床治疗的新时代。本文介绍了磁性四氧化三铁粒子的化学制备方法,包括共沉淀法、溶胶-凝胶法、微乳液法,并对各种方法的优缺点进行了比较;重点阐述了磁性壳聚糖,磁性聚乳酸,磁性PEG,磁性PCL复合材料的制备,及它们在酶的固定化、磁靶向药物及基因载体等医学领域的应用,显示了Fe3O4/生物可降解复合材料在医学领域的广阔应用前景;最后对复合材料走向临床应用所面临的问题及发展前景进行了讨论。 相似文献
109.
An empirically based alternative to DSM-5's disruptive mood dysregulation disorder for ICD-11
下载免费PDF全文
![点击此处可从《World psychiatry》网站下载免费的PDF全文](/ch/ext_images/free.gif)
110.
The focus of the present investigation was to explore the use of solid-state nuclear magnetic resonance (13C ssNMR) and X-ray powder diffraction (XRPD) for quantification of nimodipine polymorphs (form I and form II) crystallized in a cosolvent formulation. The cosolvent formulation composed of polyethylene glycol 400, glycerin, water, and 2.5% drug, and was stored at 5°C for the drug crystallization. The 13C ssNMR and XRPD data of the sample matrices containing varying percentages of nimodipine form I and form II were collected. Univariate and multivariate models were developed using the data. Least square method was used for the univariate model generation. Partial least square and principle component regressions were used for the multivariate models development. The univariate models of the 13C ssNMR were better than the XRPD as indicated by statistical parameters such as correlation coefficient, R2, root mean square error, and standard error. On the other hand, the XRPD multivariate models were better than the 13C ssNMR as indicated by precision and accuracy parameters. Similar values were predicted by the univariate and multivariate models for independent samples. In conclusion, the univariate and multivariate models of 13C ssNMR and XRPD can be used to quantitate nimodipine polymorphs.KEY WORDS: nimodipine polymorphs, X-ray powder diffraction, solid-state nuclear magnetic resonance, univariate, multivariate 相似文献