全文获取类型
收费全文 | 1956篇 |
免费 | 141篇 |
国内免费 | 5篇 |
出版年
2023年 | 7篇 |
2022年 | 40篇 |
2021年 | 68篇 |
2020年 | 49篇 |
2019年 | 58篇 |
2018年 | 61篇 |
2017年 | 53篇 |
2016年 | 81篇 |
2015年 | 91篇 |
2014年 | 131篇 |
2013年 | 115篇 |
2012年 | 171篇 |
2011年 | 147篇 |
2010年 | 110篇 |
2009年 | 84篇 |
2008年 | 136篇 |
2007年 | 132篇 |
2006年 | 119篇 |
2005年 | 93篇 |
2004年 | 108篇 |
2003年 | 81篇 |
2002年 | 72篇 |
2001年 | 8篇 |
2000年 | 12篇 |
1999年 | 9篇 |
1998年 | 17篇 |
1997年 | 14篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有2102条查询结果,搜索用时 31 毫秒
111.
Fahrni JF Bolivar I Berney C Nassonova E Smirnov A Pawlowski J 《Molecular biology and evolution》2003,20(11):1881-1886
Lobose amoebae are abundant free-living protists and important pathogenic agents, yet their evolutionary history and position in the universal tree of life are poorly known. Molecular data for lobose amoebae are limited to a few species, and all phylogenetic studies published so far lacked representatives of many of their taxonomic groups. Here we analyze actin and small-subunit ribosomal RNA (SSU rRNA) gene sequences of a broad taxon sampling of naked, lobose amoebae. Our results support the existence of a monophyletic Amoebozoa clade, which comprises all lobose amoebae examined so far, the amitochondriate pelobionts and entamoebids, and the slime molds. Both actin and SSU rRNA phylogenies distinguish two well-defined clades of amoebae, the "Gymnamoebia sensu stricto" and the Archamoebae (pelobionts + entamoebids), and one weakly supported and ill-resolved group comprising some naked, lobose amoebae and the Mycetozoa. 相似文献
112.
113.
Lehmann C Lim K Chalamasetty VR Krajewski W Melamud E Galkin A Howard A Kelman Z Reddy PT Murzin AG Herzberg O 《Proteins》2003,50(2):249-260
The crystal structure of HI0074 from Haemophilus influenzae, a protein of unknown function, has been determined at a resolution of 2.4 A. The molecules form an up-down, four-helix bundle, and associate into homodimers. The fold is most closely related to the substrate-binding domain of KNTase, yet the amino acid sequences of the two proteins exhibit no significant homology. Sequence analyses of completely and incompletely sequenced genomes reveal that the two adjacent genes, HI0074 and HI0073, and their close relatives comprise a new family of nucleotidyltransferases, with 15 members at the time of writing. The analyses also indicate that this is one of eight families of a large nucleotidyltransferase superfamily, whose members were identified based on the proximity of the nucleotide- and substrate-binding domains on the respective genomes. Both HI0073 and HI0074 were annotated "hypothetical" in the original genome sequencing publication. HI0073 was cloned, expressed, and purified, and was shown to form a complex with HI0074 by polyacrylamide gel electrophoresis under nondenaturing conditions, analytic size exclusion chromatography, and dynamic light scattering. Double- and single-stranded DNA binding assays showed no evidence of DNA binding to HI0074 or to HI0073/HI0074 complex despite the suggestive shape of the putative binding cleft formed by the HI0074 dimer. 相似文献
114.
Jane?E?LadnerEmail author Galina?Obmolova Alexey?Teplyakov Andrew?J?Howard Pavel?P?Khil R?Daniel?Camerini-Otero Gary?L?Gilliland 《BMC structural biology》2003,3(1):7
Background
The protein encoded by the gene ybgI was chosen as a target for a structural genomics project emphasizing the relation of protein structure to function.Results
The structure of the ybgI protein is a toroid composed of six polypeptide chains forming a trimer of dimers. Each polypeptide chain binds two metal ions on the inside of the toroid.Conclusion
The toroidal structure is comparable to that of some proteins that are involved in DNA metabolism. The di-nuclear metal site could imply that the specific function of this protein is as a hydrolase-oxidase enzyme.115.
Hodgson DM Zingman LV Kane GC Perez-Terzic C Bienengraeber M Ozcan C Gumina RJ Pucar D O'Coclain F Mann DL Alekseev AE Terzic A 《The EMBO journal》2003,22(8):1732-1742
ATP-sensitive potassium (K(ATP)) channels are required for maintenance of homeostasis during the metabolically demanding adaptive response to stress. However, in disease, the effect of cellular remodeling on K(ATP) channel behavior and associated tolerance to metabolic insult is unknown. Here, transgenic expression of tumor necrosis factor alpha induced heart failure with typical cardiac structural and energetic alterations. In this paradigm of disease remodeling, K(ATP) channels responded aberrantly to metabolic signals despite intact intrinsic channel properties, implicating defects proximal to the channel. Indeed, cardiomyocytes from failing hearts exhibited mitochondrial and creatine kinase deficits, and thus a reduced potential for metabolic signal generation and transmission. Consequently, K(ATP) channels failed to properly translate cellular distress under metabolic challenge into a protective membrane response. Failing hearts were excessively vulnerable to metabolic insult, demonstrating cardiomyocyte calcium loading and myofibrillar contraction banding, with tolerance improved by K(ATP) channel openers. Thus, disease-induced K(ATP) channel metabolic dysregulation is a contributor to the pathobiology of heart failure, illustrating a mechanism for acquired channelopathy. 相似文献
116.
Volume Contents
Contents Volume 26 (2000) 相似文献117.
118.
Rho-mediated Contractility Exposes a Cryptic Site in Fibronectin and Induces Fibronectin Matrix Assembly 总被引:19,自引:2,他引:17
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Cuiling Zhong Magdalena Chrzanowska-Wodnicka James Brown Amy Shaub Alexey M. Belkin Keith Burridge 《The Journal of cell biology》1998,141(2):539-551
Many factors influence the assembly of fibronectin into an insoluble fibrillar extracellular matrix. Previous work demonstrated that one component in serum that promotes the assembly of fibronectin is lysophosphatidic acid (Zhang, Q., W.J. Checovich, D.M. Peters, R.M. Albrecht, and D.F. Mosher. 1994. J. Cell Biol. 127:1447–1459). Here we show that C3 transferase, an inhibitor of the low molecular weight GTP-binding protein Rho, blocks the binding of fibronectin and the 70-kD NH2-terminal fibronectin fragment to cells and blocks the assembly of fibronectin into matrix induced by serum or lysophosphatidic acid. Microinjection of recombinant, constitutively active Rho into quiescent Swiss 3T3 cells promotes fibronectin matrix assembly by the injected cells. Investigating the mechanism by which Rho promotes fibronectin polymerization, we have used C3 to determine whether integrin activation is involved. Under conditions where C3 decreases fibronectin assembly we have only detected small changes in the state of integrin activation. However, several inhibitors of cellular contractility, that differ in their mode of action, inhibit cell binding of fibronectin and the 70-kD NH2-terminal fibronectin fragment, decrease fibronectin incorporation into the deoxycholate insoluble matrix, and prevent fibronectin's assembly into fibrils on the cell surface. Because Rho stimulates contractility, these results suggest that Rho-mediated contractility promotes assembly of fibronectin into a fibrillar matrix. One mechanism by which contractility could enhance fibronectin assembly is by tension exposing cryptic self-assembly sites within fibronectin that is being stretched. Exploring this possibility, we have found a monoclonal antibody, L8, that stains fibronectin matrices differentially depending on the state of cell contractility. L8 was previously shown to inhibit fibronectin matrix assembly (Chernousov, M.A., A.I. Faerman, M.G. Frid, O.Y. Printseva, and V.E. Koteliansky. 1987. FEBS (Fed. Eur. Biochem. Soc.) Lett. 217:124–128). When it is used to stain normal cultures that are developing tension, it reveals a matrix indistinguishable from that revealed by polyclonal anti-fibronectin antibodies. However, the staining of fibronectin matrices by L8 is reduced relative to the polyclonal antibody when the contractility of cells is inhibited by C3. We have investigated the consequences of mechanically stretching fibronectin in the absence of cells. Applying a 30–35% stretch to immobilized fibronectin induced binding of soluble fibronectin, 70-kD fibronectin fragment, and L8 monoclonal antibody. Together, these results provide evidence that self-assembly sites within fibronectin are exposed by tension. 相似文献
119.
Alexey E. Alekseev Peter A. Brady Andre Terzic 《The Journal of general physiology》1998,111(2):381-394
The mechanism by which ATP-sensitive K+ (KATP) channels open in the presence of inhibitory concentrations of ATP remains unknown. Herein, using a four-state kinetic model, we found that the nucleotide diphosphate UDP directed cardiac KATP channels to operate within intraburst transitions. These transitions are not targeted by ATP, nor the structurally unrelated sulfonylurea glyburide, which inhibit channel opening by acting on interburst transitions. Therefore, the channel remained insensitive to ATP and glyburide in the presence of UDP. “Rundown” of channel activity decreased the efficacy with which UDP could direct and maintain the channel to operate within intraburst transitions. Under this condition, the channel was sensitive to inhibition by ATP and glyburide despite the presence of UDP. This behavior of the KATP channel could be accounted for by an allosteric model of ligand-channel interaction. Thus, the response of cardiac KATP channels towards inhibitory ligands is determined by the relative lifetime the channel spends in a ligand-sensitive versus -insensitive state. Interconversion between these two conformational states represents a novel basis for KATP channel opening in the presence of inhibitory concentrations of ATP in a cardiac cell. 相似文献
120.
Alexey Fedorov Larisa Fedorova Valery Starshenko Vadim Filatov Eugeni Grigor'ev 《Journal of molecular evolution》1998,46(3):263-271
Nonrandomness in the intron and exon phase distributions in a sample of 305 human genes has been found and analyzed. It was
shown that exon duplications had a significant effect on the exon phase nonrandomness. All of the nonrandomness is probably
due to both the processes of exon duplication and shuffling. A quantitative estimation of exon duplications in the human genome
and their influence on the intron and exon phase distributions has been analyzed. According to our estimation, the proportion
of duplicated exons in the human genome constitutes at least 6% of the total. Generalizing the particular case of exon duplication
to the more common event of exon shuffling, we modeled and analyzed the influence of exon shuffling on intron phase distribution.
Received: 28 March 1997 / Accepted: 9 July 1997 相似文献