全文获取类型
收费全文 | 1178篇 |
免费 | 61篇 |
国内免费 | 1篇 |
专业分类
1240篇 |
出版年
2023年 | 11篇 |
2022年 | 20篇 |
2021年 | 28篇 |
2020年 | 23篇 |
2019年 | 26篇 |
2018年 | 40篇 |
2017年 | 28篇 |
2016年 | 44篇 |
2015年 | 62篇 |
2014年 | 94篇 |
2013年 | 104篇 |
2012年 | 118篇 |
2011年 | 105篇 |
2010年 | 56篇 |
2009年 | 57篇 |
2008年 | 87篇 |
2007年 | 60篇 |
2006年 | 54篇 |
2005年 | 50篇 |
2004年 | 37篇 |
2003年 | 34篇 |
2002年 | 28篇 |
2001年 | 5篇 |
2000年 | 6篇 |
1999年 | 10篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1960年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有1240条查询结果,搜索用时 0 毫秒
1.
Using cytogenetic analysis following Giemsa staining, nucleolar organizer region (NOR) staining, and C-banding, three distinct karyotypes in three species of curimatids belonging to the fish genus Potamorhina were identified: 2n = 54/44 M + 10 SM (P. pristigaster), 2n = 56/52 M + 2 SM + 2 ST (P. latior), and 2n = 102/2 M + 2 SM + 98 A (P. altamazonica). A 2n = 54 was considered to be the ancestral diploid number and the different karyotypes were probably the result of centric fissions. Both the NOR pattern and constitutive heterochromatin pattern are species specific. 相似文献
2.
3.
Catarina E. Hioe Denise M. McKinney Jeffrey A. Frelinger Minnie McMillan 《Immunogenetics》1994,40(3):222-229
In order to investigate the role of residues inside and outside the peptide binding cleft of the L2 molecule in peptide presentation to cytotoxic T lymphocytes (CTL), we constructed a series of point mutations in the L
d
gene. We determined the effects of the mutations in the Ld molecule on the binding and recognition of an Ld-restricted CTL epitope derived from the nucleoprotein (NP) of the lymphocytic phoriomeningitis virus (LCMV). Each of the mutations within the Ld peptide binding cleft resulted in a complete loss of CTL recognition. Addition of the LCMV NP peptide to cells expressing these mutants did not increase surface Ld expression, suggesting that the mutations altered peptide binding. Mutations involving pockets D and E within the cleft affected LCMV peptide binding and recognition as drastically as those in pocket B, which was predicted to interact with a main anchor residue of the peptide. In striking contrast, the mutations located outside the cleft did not change either recognition or binding. These results demonstrate that the Ld residues in the peptide binding cleft are the main determinants dictating LCMV NP peptide binding, and that the residues in each of the pockets within the cleft play a role in this interaction. Surprisingly, one mutation outside the peptide binding cleft, T92S, abrogated CTL lysis of target cells treated with the LCMV NP peptide, but not virus-infected cells. These data show that this mutation selectively altered the presentation of the LCMV NP peptide introduced to the cell exogenously, but not endogenously. This implies that the pathway by which peptides associate with class I molecules within the cell differs from that of exogenous peptide binding. 相似文献
4.
5.
Joana Pais De Faria Vitor H. Paiva Sara N. Veríssimo Catarina S. Lopes Rita Soares João Oliveira Ivo dos Santos Ana C. Norte Jaime A. Ramos 《Ibis》2023,165(1):312-321
Gulls, as largely flexible opportunistic individuals, have been increasingly breeding in many cities around the world, but it is still unclear whether urban habitats are of equal or higher quality than traditional natural habitats or represent an ecological trap with immediate reproductive benefits but longer-term detrimental consequences to health. Here we present a study of breeding parameters (nest density, egg dimensions, clutch size, hatching success and adult body condition) and physiological parameters (erythrocyte sedimentation rate, heterophil/lymphocyte ratio, haemoglobin concentration and measurements of oxidative stress) as indicators of the general health condition of Yellow-legged Gull Larus michahellis adults and chicks from natural and urban colonies. Yellow-legged Gulls in the largest urban area (Porto) laid smaller eggs and clutches, showed a significantly lower occurrence of inflammatory processes in chicks, and showed a slower early chick growth than in the natural colony of Deserta. This suggests that urban gulls might be facing important trade-offs between the advantages of breeding in lower density urban colonies, with fewer intraspecific interactions and a lower disease transmission probability, and the disadvantages of having an anthropogenic diet usually lower in nutritional value. 相似文献
6.
7.
Graça Soveral Catarina Prista Teresa F. Moura Maria C. Loureiro‐Dias 《Biology of the cell / under the auspices of the European Cell Biology Organization》2011,103(1):35-54
In yeast, the presence of orthodox aquaporins has been first recognized in Saccharomyces cerevisiae, in which two genes (AQY1 and AQY2) were shown to be related to mammal and plant water channels. The present review summarizes the putative orthodox aquaporin protein sequences found in available genomes of yeast and filamentous fungi. Among the 28 yeast genomes sequenced, most species present only one orthodox aquaporin, and no aquaporins were found in eight yeast species. Alignment of amino acid sequences reveals a very diverse group. Similarity values vary from 99% among species within the Saccharomyces genus to 34% between ScAqy1 and the aquaporin from Debaryomyces hansenii. All of the fungal aquaporins possess the known characteristic sequences, and residues involved in the water channel pore are highly conserved. Advances in the establishment of the structure are reviewed in relation to the mechanisms of selectivity, conductance and gating. In particular, the involvement of the protein cytosolic N‐terminus as a channel blocker preventing water flow is addressed. Methodologies used in the evaluation of aquaporin activity frequently involve the measurement of fast volume changes. Particular attention is paid to data analysis to obtain accurate membrane water permeability parameters. Although the presence of aquaporins clearly enhances membrane water permeability, the relevance of these ubiquitous water channels in yeast performance remains obscure. 相似文献
8.
Isabel C.M. Fensterseifer Mário R. Felício Eliane S.F. Alves Marlon H. Cardoso Marcelo D.T. Torres Carolina O. Matos Osmar N. Silva Timothy K. Lu Maurício V. Freire Natan C. Neves Sónia Gonçalves Luciano M. Lião Nuno C. Santos William F. Porto Cesar de la Fuente-Nunez Octavio L. Franco 《生物化学与生物物理学报:生物膜》2019,1861(7):1375-1387
Infections caused by Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa foremost among them, constitute a major worldwide health problem. Bioinformatics methodologies are being used to rationally design new antimicrobial peptides, a potential alternative for treating these infections. One of the algorithms used to develop antimicrobial peptides is the Joker, which was used to design the peptide PaDBS1R6. This study evaluates the antibacterial activities of PaDBS1R6 in vitro and in vivo, characterizes the peptide interaction to target membranes, and investigates the PaDBS1R6 structure in contact with mimetic vesicles. Moreover, we demonstrate that PaDBS1R6 exhibits selective antimicrobial activity against Gram-negative bacteria. In the presence of negatively charged and zwitterionic lipids the structural arrangement of PaDBS1R6 transits from random coil to α-helix, as characterized by circular dichroism. The tertiary structure of PaDBS1R6 was determined by NMR in zwitterionic dodecylphosphocholine (DPC) micelles. In conclusion, PaDBS1R6 is a candidate for the treatment of nosocomial infections caused by Gram-negative bacteria, as template for producing other antimicrobial agents. 相似文献
9.
Robo4 maintains vessel integrity and inhibits angiogenesis by interacting with UNC5B 总被引:1,自引:0,他引:1
Koch AW Mathivet T Larrivée B Tong RK Kowalski J Pibouin-Fragner L Bouvrée K Stawicki S Nicholes K Rathore N Scales SJ Luis E del Toro R Freitas C Bréant C Michaud A Corvol P Thomas JL Wu Y Peale F Watts RJ Tessier-Lavigne M Bagri A Eichmann A 《Developmental cell》2011,20(1):33-46
Robo4 is an endothelial cell-specific member of the Roundabout axon guidance receptor family. To identify Robo4 binding partners, we performed a protein-protein interaction screen with the Robo4 extracellular domain. We find that Robo4 specifically binds to UNC5B, a vascular Netrin receptor, revealing unexpected interactions between two endothelial guidance receptors. We show that Robo4 maintains vessel integrity by activating UNC5B, which inhibits signaling downstream of vascular endothelial growth factor (VEGF). Function-blocking monoclonal antibodies against Robo4 and UNC5B increase angiogenesis and disrupt vessel integrity. Soluble Robo4 protein inhibits VEGF-induced vessel permeability and rescues barrier defects in Robo4(-/-) mice, but not in mice treated with anti-UNC5B. Thus, Robo4-UNC5B signaling maintains vascular integrity by counteracting VEGF signaling in endothelial cells, identifying a novel function of guidance receptor interactions in the vasculature. 相似文献
10.
Dean E. Hammond Deborah M. Simpson Catarina Franco Marina Wright Muelas John Waters R.W. Ludwig Mark C. Prescott Jane L. Hurst Robert J. Beynon Edward Lau 《Molecular & cellular proteomics : MCP》2022,21(7):100252
Changes in the abundance of individual proteins in the proteome can be elicited by modulation of protein synthesis (the rate of input of newly synthesized proteins into the protein pool) or degradation (the rate of removal of protein molecules from the pool). A full understanding of proteome changes therefore requires a definition of the roles of these two processes in proteostasis, collectively known as protein turnover. Because protein turnover occurs even in the absence of overt changes in pool abundance, turnover measurements necessitate monitoring the flux of stable isotope–labeled precursors through the protein pool such as labeled amino acids or metabolic precursors such as ammonium chloride or heavy water. In cells in culture, the ability to manipulate precursor pools by rapid medium changes is simple, but for more complex systems such as intact animals, the approach becomes more convoluted. Individual methods bring specific complications, and the suitability of different methods has not been comprehensively explored. In this study, we compare the turnover rates of proteins across four mouse tissues, obtained from the same inbred mouse strain maintained under identical husbandry conditions, measured using either [13C6]lysine or [2H2]O as the labeling precursor. We show that for long-lived proteins, the two approaches yield essentially identical measures of the first-order rate constant for degradation. For short-lived proteins, there is a need to compensate for the slower equilibration of lysine through the precursor pools. We evaluate different approaches to provide that compensation. We conclude that both labels are suitable, but careful determination of precursor enrichment kinetics in amino acid labeling is critical and has a considerable influence on the numerical values of the derived protein turnover rates. 相似文献