全文获取类型
收费全文 | 6673篇 |
免费 | 638篇 |
国内免费 | 2篇 |
出版年
2023年 | 38篇 |
2022年 | 74篇 |
2021年 | 127篇 |
2020年 | 90篇 |
2019年 | 113篇 |
2018年 | 166篇 |
2017年 | 127篇 |
2016年 | 227篇 |
2015年 | 400篇 |
2014年 | 421篇 |
2013年 | 491篇 |
2012年 | 630篇 |
2011年 | 570篇 |
2010年 | 372篇 |
2009年 | 308篇 |
2008年 | 403篇 |
2007年 | 400篇 |
2006年 | 353篇 |
2005年 | 326篇 |
2004年 | 353篇 |
2003年 | 303篇 |
2002年 | 271篇 |
2001年 | 50篇 |
2000年 | 49篇 |
1999年 | 64篇 |
1998年 | 87篇 |
1997年 | 45篇 |
1996年 | 30篇 |
1995年 | 47篇 |
1994年 | 34篇 |
1993年 | 31篇 |
1992年 | 38篇 |
1991年 | 17篇 |
1990年 | 20篇 |
1989年 | 21篇 |
1988年 | 22篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 14篇 |
1984年 | 10篇 |
1983年 | 17篇 |
1982年 | 17篇 |
1981年 | 12篇 |
1980年 | 12篇 |
1979年 | 6篇 |
1978年 | 11篇 |
1977年 | 7篇 |
1976年 | 9篇 |
1974年 | 12篇 |
1968年 | 5篇 |
排序方式: 共有7313条查询结果,搜索用时 234 毫秒
311.
Molecular requirements for the regulation of the renal outer medullary K(+) channel ROMK1 by the serum- and glucocorticoid-inducible kinase SGK1 总被引:3,自引:0,他引:3
Palmada M Embark HM Yun C Böhmer C Lang F 《Biochemical and biophysical research communications》2003,311(3):629-634
The serum- and glucocorticoid- inducible kinase SGK1 stimulates the renal outer medullary K(+) channel ROMK1 in the presence of the Na(+)/H(+) exchanger regulating factor NHERF2. SGK1/NHERF2 are effective through enhancement of ROMK1 abundance within the cell membrane. The present study aims to define the molecular requirements for the interaction of ROMK1 with SGK1/NHERF2. Pull down assays reveal that SGK1 interacts with NHERF2 through the second PDZ domain of NHERF2. According to chemiluminescence and electrophysiology, deletion of the second PDZ domain of NHERF2 or the putative PDZ binding motif on ROMK1 abrogates the stimulating effect of SGK1 on ROMK1 protein abundance in the plasma membrane and K(+) current. 相似文献
312.
313.
This numerical study evaluates the momentum and mass transfer in an immobilized enzyme reactor. The simulation is based on the solution of the three-dimensional Navier-Stokes equation and a scalar transport equation with a sink term for the transport and the conversion of substrate to product. The reactor consists of a container filled with 20 spherical enzyme carriers. Each of these carriers is covered with an active enzyme layer where the conversion takes place. To account for the biochemical activity, the sink term in the scalar transport equation is represented by a standard Michaelis-Menten approach. The simulation gives detailed information of the local substrate and product concentrations with respect to external and internal transport limitations. A major focus is set on the influence of the substrate transport velocity on the catalytic process. For reactor performance analysis the overall and the local transport processes are described by a complete set of dimensionless variables. The interaction between substrate concentration, velocity, and efficiency of the process can be studied with the help of these variables. The effect of different substrate inflow concentrations on the process can be seen in relation to velocity variations. The flow field characterization of the system makes it possible to understand fluid mechanical properties and its importance to transport processes. The distribution of fluid motion through the void volume has different properties in different parts of the reactor. This phenomenon has strong effects on the arrangement of significantly different mass transport areas as well as on process effectiveness. With the given data it is also possible to detect zones of high, low, and latent enzymatic activity and to determine whether the conversion is limited due to mass transfer or reaction resistances. 相似文献
314.
Composition,acquisition, and distribution of the Vi exopolysaccharide-encoding Salmonella enterica pathogenicity island SPI-7 下载免费PDF全文
Pickard D Wain J Baker S Line A Chohan S Fookes M Barron A Gaora PO Chabalgoity JA Thanky N Scholes C Thomson N Quail M Parkhill J Dougan G 《Journal of bacteriology》2003,185(17):5055-5065
Vi capsular polysaccharide production is encoded by the viaB locus, which has a limited distribution in Salmonella enterica serovars. In S. enterica serovar Typhi, viaB is encoded on a 134-kb pathogenicity island known as SPI-7 that is located between partially duplicated tRNA(pheU) sites. Functional and bioinformatic analysis suggests that SPI-7 has a mosaic structure and may have evolved as a consequence of several independent insertion events. Analysis of viaB-associated DNA in Vi-positive S. enterica serovar Paratyphi C and S. enterica serovar Dublin isolates revealed the presence of similar SPI-7 islands. In S. enterica serovars Paratyphi C and Dublin, the SopE bacteriophage and a 15-kb fragment adjacent to the intact tRNA(pheU) site were absent. In S. enterica serovar Paratyphi C only, a region encoding a type IV pilus involved in the adherence of S. enterica serovar Typhi to host cells was missing. The remainder of the SPI-7 islands investigated exhibited over 99% DNA sequence identity in the three serovars. Of 30 other Salmonella serovars examined, 24 contained no insertions at the equivalent tRNA(pheU) site, 2 had a 3.7-kb insertion, and 4 showed sequence variation at the tRNA(pheU)-phoN junction, which was not analyzed further. Sequence analysis of the SPI-7 region from S. enterica serovar Typhi strain CT18 revealed significant synteny with clusters of genes from a variety of saprophytic bacteria and phytobacteria, including Pseudomonas aeruginosa and Xanthomonas axonopodis pv. citri. This analysis suggested that SPI-7 may be a mobile element, such as a conjugative transposon or an integrated plasmid remnant. 相似文献
315.
Qiao D Meyer K Mundhenke C Drew SA Friedl A 《The Journal of biological chemistry》2003,278(18):16045-16053
Fibroblast growth factor-2 (FGF2) is a potent angiogenic factor in gliomas. Heparan sulfate promotes ligand binding to receptor tyrosine kinase and regulates signaling. The goal of this study was to examine the contribution of heparan sulfate proteoglycans (HSPGs) to glioma angiogenesis. Here we show that all brain endothelial cell HSPGs carry heparan sulfate chains similarly capable of forming a ternary complex with FGF2 and fibroblast growth factor receptor-1c and of promoting a mitogenic signal. Immunohistochemical analysis revealed that glypican-1 was overexpressed in glioma vessel endothelial cells, whereas this cell-surface HSPG was consistently undetectable in normal brain vessels. To determine the effect of increased glypican-1 expression on FGF2 signaling, we transfected normal brain endothelial cells, which express low base-line levels of glypican-1, with this proteoglycan. Glypican-1 expression enhanced growth of brain endothelial cells and sensitized them to FGF2-induced mitogenesis despite the fact that glypican-1 remained a minor proteoglycan. In contrast, overexpression of syndecan-1 had no effect on growth or FGF2 sensitivity. We conclude that the glypican-1 core protein has a specific role in FGF2 signaling. Glypican-1 overexpression may contribute to angiogenesis and the radiation resistance characteristic of this malignancy. 相似文献
316.
Callebaut I Curcio-Morelli C Mornon JP Gereben B Buettner C Huang S Castro B Fonseca TL Harney JW Larsen PR Bianco AC 《The Journal of biological chemistry》2003,278(38):36887-36896
The three iodothyronine selenodeiodinases catalyze the initiation and termination of thyroid hormone effects in vertebrates. Structural analyses of these proteins have been hindered by their integral membrane nature and the inefficient eukaryotic-specific pathway for selenoprotein synthesis. Hydrophobic cluster analysis used in combination with Position-specific Iterated BLAST reveals that their extramembrane portion belongs to the thioredoxin-fold superfamily for which experimental structure information exists. Moreover, a large deiodinase region imbedded in the thioredoxin fold shares strong similarities with the active site of iduronidase, a member of the clan GH-A-fold of glycoside hydrolases. This model can explain a number of results from previous mutagenesis analyses and permits new verifiable insights into the structural and functional properties of these enzymes. 相似文献
317.
318.
Schaer DJ Boretti FS Hongegger A Poehler D Linnscheid P Staege H Müller C Schoedon G Schaffner A 《Immunogenetics》2001,53(2):170-177
319.
Claudins create charge-selective channels in the paracellular pathway between epithelial cells 总被引:20,自引:0,他引:20
Colegio OR Van Itallie CM McCrea HJ Rahner C Anderson JM 《American journal of physiology. Cell physiology》2002,283(1):C142-C147
Epithelia separate tissuespaces by regulating the passage of ions, solutes, and water throughboth the transcellular and paracellular pathways. Paracellularpermeability is defined by intercellular tight junctions, which varywidely among tissues with respect to solute flux, electricalresistance, and ionic charge selectivity. To test the hypothesis thatmembers of the claudin family of tight junction proteins create chargeselectivity, we assessed the effect of reversing the charge of selectedextracellular amino acids in two claudins using site-directedmutagenesis. Claudins were expressed in cultured Madin-Darby caninekidney cell monolayers under an inducible promoter, and clones werecompared with and without induction for transmonolayer electricalresistance and dilution potentials. Expression and localization ofclaudins were determined by immunoblotting, immunofluorescencemicroscopy, and freeze-fracture electron microscopy. We observed thatsubstituting a negative for a positive charge at position 65 in thefirst extracellular domain of claudin-4 increased paracellularNa+ permeability. Conversely, substituting positive fornegative charges at three positions in the first extracellular domainof claudin-15, singly and in combination, reversed paracellular charge selectivity from a preference for Na+ to Cl.These results support a model where claudins create charge-selective channels in the paracellular space. 相似文献
320.