全文获取类型
收费全文 | 646篇 |
免费 | 77篇 |
专业分类
723篇 |
出版年
2023年 | 5篇 |
2022年 | 6篇 |
2021年 | 22篇 |
2020年 | 10篇 |
2019年 | 9篇 |
2018年 | 19篇 |
2017年 | 18篇 |
2016年 | 21篇 |
2015年 | 35篇 |
2014年 | 42篇 |
2013年 | 37篇 |
2012年 | 50篇 |
2011年 | 40篇 |
2010年 | 31篇 |
2009年 | 34篇 |
2008年 | 35篇 |
2007年 | 35篇 |
2006年 | 39篇 |
2005年 | 37篇 |
2004年 | 26篇 |
2003年 | 23篇 |
2002年 | 24篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 12篇 |
1998年 | 8篇 |
1997年 | 3篇 |
1996年 | 8篇 |
1995年 | 7篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1991年 | 6篇 |
1990年 | 9篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1985年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1977年 | 2篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1964年 | 2篇 |
1961年 | 3篇 |
1960年 | 2篇 |
1930年 | 1篇 |
1926年 | 1篇 |
1908年 | 1篇 |
1905年 | 1篇 |
排序方式: 共有723条查询结果,搜索用时 15 毫秒
101.
Ranaivoson FM Antoine M Kauffmann B Boschi-Muller S Aubry A Branlant G Favier F 《Journal of molecular biology》2008,377(1):268-280
The methionine sulfoxide reductases (Msrs) are thioredoxin-dependent oxidoreductases that catalyse the reduction of the sulfoxide function of the oxidized methionine residues. These enzymes have been shown to regulate the life span of a wide range of microbial and animal species and to play the role of physiological virulence determinant of some bacterial pathogens. Two structurally unrelated classes of Msrs exist, MsrA and MsrB, with opposite stereoselectivity towards the R and S isomers of the sulfoxide function, respectively. Both Msrs share a similar three-step chemical mechanism including (1) the formation of a sulfenic acid intermediate on the catalytic Cys with the concomitant release of the product—methionine, (2) the formation of an intramonomeric disulfide bridge between the catalytic and the regenerating Cys and (3) the reduction of the disulfide bridge by thioredoxin or its homologues. In this study, four structures of the MsrA domain of the PilB protein from Neisseria meningitidis, representative of four catalytic intermediates of the MsrA catalytic cycle, were determined by X-ray crystallography: the free reduced form, the Michaelis-like complex, the sulfenic acid intermediate and the disulfide oxidized forms. They reveal a conserved overall structure up to the formation of the sulfenic acid intermediate, while a large conformational switch is observed in the oxidized form. The results are discussed in relation to those proposed from enzymatic, NMR and theoretical chemistry studies. In particular, the substrate specificity and binding, the catalytic scenario of the reductase step and the relevance and role of the large conformational change observed in the oxidized form are discussed. 相似文献
102.
Joubès J Raffaele S Bourdenx B Garcia C Laroche-Traineau J Moreau P Domergue F Lessire R 《Plant molecular biology》2008,67(5):547-566
As precursors of wax compounds, very long chain fatty acids participate in the limitation of non-stomatal water loss and the prevention of pathogen attacks. They also serve as energy storage in seeds and as membrane building blocks. Their biosynthesis is catalyzed by the acyl-CoA elongase, a membrane-bound enzymatic complex containing four distinct enzymes (KCS, KCR, HCD and ECR). Twenty-one 3-ketoacyl-CoA synthase (KCS) genes have been identified in Arabidopsis thaliana genome. In this paper we present an overview of the acyl-CoA elongase genes in Arabidopsis focusing on the entire KCS family. We show that the KCS family is made up of 8 distinct subclasses, according to their phylogeny, duplication history, genomic organization, protein topology and 3D modelling. The analysis of the subcellular localization in tobacco cells of the different subunits of the acyl-CoA elongase shows that all these proteins are localized in the endoplasmic reticulum demonstrating that VLCFA production occurs in this compartment. The expression patterns in Arabidopsis of the acyl-CoA elongase genes suggest several levels of regulations at the tissular or organ level but also under stress conditions suggesting a complex organization of this multigenic family. 相似文献
103.
Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions 总被引:4,自引:0,他引:4
Polymorphonuclear neutrophils form a primary line of defense against bacterial infections using complementary oxidative and non-oxidative pathways to destroy phagocytized pathogens. The three serine proteases elastase, proteinase 3 and cathepsin G, are major components of the neutrophil primary granules that participate in the non-oxidative pathway of intracellular pathogen destruction. Neutrophil activation and degranulation results in the release of these proteases into the extracellular medium as proteolytically active enzymes, part of them remaining exposed at the cell surface. Extracellular neutrophil serine proteases also help kill bacteria and are involved in the degradation of extracellular matrix components during acute and chronic inflammation. But they are also important as specific regulators of the immune response, controlling cellular signaling through the processing of chemokines, modulating the cytokine network, and activating specific cell surface receptors. Neutrophil serine proteases are also involved in the pathogenicity of a variety of human diseases. This review focuses on the structural and functional properties of these proteases that may explain their specific biological roles, and facilitate their use as molecular targets for new therapeutic strategies. 相似文献
104.
105.
106.
Cell walls prepared from aged discs by extraction in 0·1 M acetate buffer, pH 4·8, possess ionically bound acid invertase which can be removed from the wall by incubation in 1 M sodium chloride in 0·1 M acetate buffer, pH 4·8, and more firmly attached enzyme which is not removed. Cell walls prepared in 0·195 M phosphate-0·003 M citrate-buffer, pH 8·0, do not possess ionically bound enzyme. Ionically bound invertase is density labelled when discs are aged in 90% deuterium oxide suggesting that at least part of the increase in activity observed during aging is due to de novo protein synthesis. 相似文献
107.
108.
Alex Eyraud Pierre Tattevin Svetlana Chabelskaya Brice Felden 《Nucleic acids research》2014,42(8):4892-4905
The emergence of Staphylococcus aureus strains that are resistant to glycopeptides has led to alarming scenarios where serious staphylococcal infections cannot be treated. The bacterium expresses many small regulatory RNAs (sRNAs) that have unknown biological functions for the most part. Here we show that an S. aureus sRNA, SprX (alias RsaOR), shapes bacterial resistance to glycopeptides, the invaluable treatments for Methicillin-resistant staphylococcal infections. Modifying SprX expression levels influences Vancomycin and Teicoplanin glycopeptide resistance. Comparative proteomic studies have identified that SprX specifically downregulates stage V sporulation protein G, SpoVG. SpoVG is produced from the yabJ-spoVG operon and contributes to S. aureus glycopeptide resistance. SprX negatively regulates SpoVG expression by direct antisense pairings at the internal translation initiation signals of the second operon gene, without modifying bicistronic mRNA expression levels or affecting YabJ translation. The SprX and yabJ-spoVG mRNA domains involved in the interaction have been identified, highlighting the importance of a CU-rich loop of SprX in the control of SpoVG expression. We have shown that SpoVG might not be the unique SprX target involved in the glycopeptide resistance and demonstrated that the regulation of glycopeptide sensitivity involves the CU-rich domain of SprX. Here we report the case of a sRNA influencing antibiotic resistance of a major human pathogen. 相似文献
109.
110.
Aprilianto E. Wiria Firdaus Hamid Linda J. Wammes Maria M. M. Kaisar Linda May Margaretta A. Prasetyani Sitti Wahyuni Yenny Djuardi Iwan Ariawan Heri Wibowo Bertrand Lell Robert Sauerwein Gary T. Brice Inge Sutanto Lisette van Lieshout Anton J. M. de Craen Ronald van Ree Jaco J. Verweij Roula Tsonaka Jeanine J. Houwing-Duistermaat Adrian J. F. Luty Erliyani Sartono Taniawati Supali Maria Yazdanbakhsh 《PloS one》2013,8(3)