全文获取类型
收费全文 | 838篇 |
免费 | 120篇 |
出版年
2021年 | 9篇 |
2018年 | 12篇 |
2016年 | 12篇 |
2015年 | 24篇 |
2014年 | 24篇 |
2013年 | 46篇 |
2012年 | 41篇 |
2011年 | 48篇 |
2010年 | 33篇 |
2009年 | 35篇 |
2008年 | 39篇 |
2007年 | 26篇 |
2006年 | 28篇 |
2005年 | 33篇 |
2004年 | 28篇 |
2003年 | 27篇 |
2002年 | 24篇 |
2001年 | 38篇 |
2000年 | 31篇 |
1999年 | 33篇 |
1998年 | 19篇 |
1997年 | 18篇 |
1996年 | 10篇 |
1995年 | 13篇 |
1994年 | 8篇 |
1993年 | 11篇 |
1992年 | 19篇 |
1991年 | 27篇 |
1990年 | 10篇 |
1989年 | 21篇 |
1988年 | 17篇 |
1987年 | 12篇 |
1986年 | 20篇 |
1985年 | 12篇 |
1984年 | 14篇 |
1983年 | 7篇 |
1982年 | 20篇 |
1981年 | 8篇 |
1979年 | 4篇 |
1978年 | 10篇 |
1977年 | 10篇 |
1976年 | 7篇 |
1975年 | 6篇 |
1974年 | 4篇 |
1973年 | 9篇 |
1972年 | 7篇 |
1971年 | 16篇 |
1970年 | 4篇 |
1969年 | 7篇 |
1967年 | 3篇 |
排序方式: 共有958条查询结果,搜索用时 343 毫秒
41.
42.
43.
Richard B Sherley Robert JM Crawford Bruce M Dyer Jessica Kemper Azwianewi B Makhado Makhudu Masotla 《Ostrich》2019,90(4):335-346
The Cape Gannet Morus capensis is one of several seabird species endemic to the Benguela upwelling ecosystem (BUS) but whose population has recently decreased, leading to an unfavourable IUCN Red List assessment. Application of ‘JARA’ (‘Just Another Red-List Assessment,’ a Bayesian state-space tool used for IUCN Red List assessments) to updated information on the areas occupied by Cape Gannets and the nest densities of breeding birds at their six colonies, suggested that the species should be classified as Vulnerable. However, the rate of decrease of Cape Gannets in their most-recent generation exceeded that of the previous generation, primarily as a result of large decreases at Bird Island, Lambert’s Bay, and Malgas Island, off South Africa’s west coast (the western part of their range). Since the 1960s, there has been an ongoing redistribution of the species from northwest to southeast around southern Africa, and ~70% of the population now occurs on the south coast of South Africa, at Bird Island in Algoa Bay, on the eastern border of the BUS. Recruitment rather than adult survival may be limiting the present population; however, information on the seabird’s demographic parameters and mortality in fisheries is lacking for colonies in the northern part of the BUS. Presently, major threats to Cape Gannet include: substantially decreased availability of their preferred prey in the west; heavy mortalities of eggs, chicks and fledglings at and around colonies, inflicted by Cape Fur Seals Arctocephalus pusillus and other seabirds; substantial disturbance at colonies caused by Cape Fur Seals attacking adult gannets ashore; oiling; and disease. 相似文献
44.
The mitogen-activated protein (MAP) kinase ERK2 is an essential signal transduction molecule that mediates extracellular signaling by all polypeptide growth factors. Full activation of ERK2 requires phosphorylation at both a threonine residue (Thr(183)) conserved in most protein kinases as well as a tyrosine residue (Tyr(185)) unique to members of the mitogen-activated protein kinase family. We have characterized the kinetic role of phosphorylation at each site with respect to the overall activation mechanism, providing a complete picture of the reaction steps involved. Phosphorylation at Tyr(185) serves to configure the ATP binding site, while phosphorylation at both residues is required to stabilize binding of the protein substrate, myelin basic protein. Similar control mechanisms are employed to stabilize ATP and myelin basic protein in the phosphoryl group transfer reaction, accounting for the enormous increase in turnover rate. The mechanism of ERK2 activation is kinetically similar to that of the cell cycle control protein, cdk2/cyclinA. Phosphorylation of Tyr(185) in ERK2 and association of cyclinA with cdk2 both serve to stabilize ATP binding. Subsequent phosphorylation of both enzymes on threonine serves to stabilize binding of the phosphoacceptor substrate. 相似文献
45.
Cell-associated ovalbumin is cross-presented much more efficiently than soluble ovalbumin in vivo 总被引:11,自引:0,他引:11
Li M Davey GM Sutherland RM Kurts C Lew AM Hirst C Carbone FR Heath WR 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(10):6099-6103
To better understand the antigenic requirements for cross-presentation, we compared the in vivo efficiency of presentation of cell-associated vs soluble OVA with the OT-I (CD8) and OT-II (CD4) TCR transgenic lines. Cross-presentation of cell-associated OVA was very efficient, requiring as little as 21 ng of OVA to activate OT-II cells and 100-fold less to activate OT-I cells. In contrast, soluble OVA was presented inefficiently, requiring at least 10,000 ng OVA for activation of either T cell subset. Thus, cell-associated OVA was presented 500-fold more efficiently than soluble OVA to CD4 T cells and 50,000-fold more efficiently to CD8 T cells. These data, which represent the first quantitative in vivo analysis of cross-presentation, show that cell-associated OVA is very efficiently presented via the class I pathway. 相似文献
46.
47.
48.
Septins form a cortical scaffold at the yeast mother-bud neck that restricts the diffusion of cortical proteins between the mother and bud and serves as a signaling center that is important for governing various cell functions. After cell cycle commitment in late G(1), septins are assembled into a narrow ring at the future bud site, which spreads to form a mature septin hourglass immediately after bud emergence. Although several septin regulators have been identified, it is unclear how they cooperate to assemble the septin scaffold. We have examined septin localization in isogenic strains containing single or multiple mutations in eight septin organization genes (CDC42, RGA1, RGA2, BEM3, CLA4, GIN4, NAP1, and ELM1). Our results suggest that these regulators act largely in parallel to promote either the initial assembly of the septin ring (CDC42, RGA1, RGA2, BEM3, and CLA4) or the conversion of the ring to a stable hourglass structure at the neck (GIN4, NAP1, and ELM1). Aberrant septin localization patterns in mutant strains could be divided into apparently discrete categories, but individual strains displayed heterogeneous defects, and there was no clear-cut correspondence between the specific mutations and specific categories of defect. These findings suggest that when they are deprived of their normal regulators, septin scaffolds collapse into a limited repertoire of aberrant states in which the nature of the mutant regulators influences the probability of a given aberrant state. 相似文献
49.
Yen TY Macher BA Bryson S Chang X Tvaroska I Tse R Takeshita S Lew AM Datti A 《The Journal of biological chemistry》2003,278(46):45864-45881
Core 2 beta1,6-N-acetylglucosaminyltransferase I (C2GnT-I) plays a pivotal role in the biosynthesis of mucin-type O-glycans that serve as ligands in cell adhesion. To elucidate the three-dimensional structure of the enzyme for use in computer-aided design of therapeutically relevant enzyme inhibitors, we investigated the participation of cysteine residues in disulfide linkages in a purified murine recombinant enzyme. The pattern of free and disulfide-bonded Cys residues was determined by liquid chromatography/electrospray ionization tandem mass spectrometry in the absence and presence of dithiothreitol. Of nine highly conserved Cys residues, under both conditions, one (Cys217) is a free thiol, and eight are engaged in disulfide bonds, with pairs formed between Cys59-Cys413, Cys100-Cys172, Cys151-Cys199, and Cys372-Cys381. The only non-conserved residue within the beta1,6-N-acetylglucosaminyltransferase family, Cys235, is also a free thiol in the presence of dithiothreitol; however, in the absence of reductant, Cys235 forms an intermolecular disulfide linkage. Biochemical studies performed with thiolreactive agents demonstrated that at least one free cysteine affects enzyme activity and is proximal to the UDP-GlcNAc binding site. A Cys217 --> Ser mutant enzyme was insensitive to thiol reactants and displayed kinetic properties virtually identical to those of the wild-type enzyme, thereby showing that Cys217, although not required for activity per se, represents the only thiol that causes enzyme inactivation when modified. Based on the pattern of free and disulfide-linked Cys residues, and a method of fold recognition/threading and homology modeling, we have computed a three-dimensional model for this enzyme that was refined using the T4 bacteriophage beta-glucosyltransferase fold. 相似文献
50.
Lew J 《Biochemistry》2003,42(4):849-856
Protein kinases constitute one of the largest enzyme families encoded by the human genome. Owing to their critical role in virtually all aspects of signal transduction, protein kinases have evolved stringent mechanisms for their regulation, which classically falls into two categories: regulation by pseudosubstrate autoinhibitory domains, and remodeling of the catalytic core in response to phosphorylation and/or protein/protein interactions. While the action of pseudosubstrate domains can be explained by simple competitive autoinhibition kinetics, it is less well understood how active site phosphorylation and/or protein/protein interactions alter rates of catalysis. Here, the kinetic basis for kinase activation is discussed in relation to the MAP kinase, ERK2, and the cyclin-dependent kinase, CDK2/cyclin A, two enzymes of central importance to mammalian cell growth and division, and which serve as prototypic models of nonautoinhibitory regulation. 相似文献