全文获取类型
收费全文 | 1950篇 |
免费 | 134篇 |
国内免费 | 4篇 |
专业分类
2088篇 |
出版年
2023年 | 17篇 |
2022年 | 40篇 |
2021年 | 44篇 |
2020年 | 22篇 |
2019年 | 35篇 |
2018年 | 57篇 |
2017年 | 38篇 |
2016年 | 52篇 |
2015年 | 76篇 |
2014年 | 108篇 |
2013年 | 138篇 |
2012年 | 169篇 |
2011年 | 161篇 |
2010年 | 108篇 |
2009年 | 87篇 |
2008年 | 121篇 |
2007年 | 140篇 |
2006年 | 104篇 |
2005年 | 124篇 |
2004年 | 105篇 |
2003年 | 92篇 |
2002年 | 90篇 |
2001年 | 11篇 |
2000年 | 7篇 |
1999年 | 16篇 |
1998年 | 20篇 |
1997年 | 18篇 |
1996年 | 17篇 |
1995年 | 11篇 |
1994年 | 11篇 |
1993年 | 6篇 |
1992年 | 8篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1978年 | 4篇 |
1976年 | 2篇 |
1969年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有2088条查询结果,搜索用时 0 毫秒
111.
The Ca(2+)-regulated photoprotein obelin was substituted at Trp92 by His, Lys, Glu, and Arg. All mutants fold into stable conformations and produce bimodal bioluminescence spectra with enhanced contribution from a violet emission. The W92R mutant has an almost monomodal bioluminescence (lambdamax=390 nm) and monomodal fluorescence (lambdamax=425 nm) of the product. Results are interpreted by an excited state proton transfer mechanism involving the substituent side group and His22 in the binding cavity. 相似文献
112.
113.
Komarova SV Pilkington MF Weidema AF Dixon SJ Sims SM 《The Journal of biological chemistry》2003,278(10):8286-8293
RANK ligand (RANKL) induces activation of NFkappaB, enhancing the formation, resorptive activity, and survival of osteoclasts. Ca(2+) transduces many signaling events, however, it is not known whether the actions of RANKL involve Ca(2+) signaling. We investigated the effects of RANKL on rat osteoclasts using microspectrofluorimetry and patch clamp. RANKL induced transient elevation of cytosolic free Ca(2+) concentration ([Ca(2+)](i)) to maxima 220 nm above basal, resulting in activation of Ca(2+)-dependent K(+) current. RANKL elevated [Ca(2+)](i) in Ca(2+)-containing and Ca(2+)-free media, and responses were prevented by the phospholipase C inhibitor. Suppression of [Ca(2+)](i) elevation using the intracellular Ca(2+) chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) abolished the ability of RANKL to enhance osteoclast survival. Using immunofluorescence, NFkappaB was found predominantly in the cytosol of untreated osteoclasts. RANKL induced transient translocation of NFkappaB to the nuclei, which was maximal at 15 min. or BAPTA delayed nuclear translocation of NFkappaB. Delays were also observed upon inhibition of calcineurin or protein kinase C. We conclude that RANKL acts through phospholipase C to release Ca(2+) from intracellular stores, accelerating nuclear translocation of NFkappaB and promoting osteoclast survival. Such cross-talk between NFkappaB and Ca(2+) signaling provides a novel mechanism for the temporal regulation of gene expression in osteoclasts and other cell types. 相似文献
114.
RESOURCERER: a database for annotating and linking microarray resources within and across species 总被引:1,自引:1,他引:0 下载免费PDF全文
Tsai J Sultana R Lee Y Pertea G Karamycheva S Antonescu V Cho J Parvizi B Cheung F Quackenbush J 《Genome biology》2001,2(11):software0002.1-software00024
Microarray expression analysis is providing unprecedented data on gene expression in humans and mammalian model systems. Although such studies provide a tremendous resource for understanding human disease states, one of the significant challenges is cross-referencing the data derived from different species, across diverse expression analysis platforms, in order to properly derive inferences regarding gene expression and disease state. To address this problem, we have developed RESOURCERER, a microarray-resource annotation and cross-reference database built using the analysis of expressed sequence tags (ESTs) and gene sequences provided by the TIGR Gene Index (TGI) and TIGR Orthologous Gene Alignment (TOGA) databases [now called Eukaryotic Gene Orthologs (EGO)]. 相似文献
115.
Davis JP Rall JA Reiser PJ Smillie LB Tikunova SB 《The Journal of biological chemistry》2002,277(51):49716-49726
The goal of this study was to examine the mechanism of magnesium binding to the regulatory domain of skeletal troponin C (TnC). The fluorescence of Trp(29), immediately preceding the first calcium-binding loop in TnC(F29W), was unchanged by addition of magnesium, but increased upon calcium binding with an affinity of 3.3 microm. However, the calcium-dependent increase in TnC(F29W) fluorescence could be reversed by addition of magnesium, with a calculated competitive magnesium affinity of 2.2 mm. When a Z acid pair was introduced into the first EF-hand of TnC(F29W), the fluorescence of G34DTnC(F29W) increased upon addition of magnesium or calcium with affinities of 295 and 1.9 microm, respectively. Addition of 3 mm magnesium decreased the calcium sensitivity of TnC(F29W) and G34DTnC(F29W) approximately 2- and 6-fold, respectively. Exchange of G34DTnC(F29W) into skinned psoas muscle fibers decreased fiber calcium sensitivity approximately 1.7-fold compared with TnC(F29W) at 1 mm [magnesium](free) and approximately 3.2-fold at 3 mm [magnesium](free). Thus, incorporation of a Z acid pair into the first EF-hand allows it to bind magnesium with high affinity. Furthermore, the data suggests that the second EF-hand, but not the first, of TnC is responsible for the competitive magnesium binding to the regulatory domain. 相似文献
116.
117.
A family of highly diverse human and mouse genes structurally links leukocyte FcR,gp42 and PECAM-1 总被引:6,自引:2,他引:4
Guselnikov SV Ershova SA Mechetina LV Najakshin AM Volkova OY Alabyev BY Taranin AV 《Immunogenetics》2002,54(2):87-95
A group of genes encoding proteins structurally related to the leukocyte Fc receptors (FcRs) and termed the IFGP family was identified in human and mouse. Sequences of four human and two mouse cDNAs predict proteins differing by domain composition. One of the mouse cDNAs encodes a secreted protein, which, in addition to four immunoglobulin (Ig)-like domains, contains a scavenger receptor superfamily-related domain at the C-terminus. The other cDNAs code for the type I transmembrane proteins with the extracellular parts comprised of one to six Ig-like domains. Five homologous types of the Ig-like domains were defined and each protein was found to have a unique combination of the domain types. The cytoplasmic tails of the transmembrane proteins show different patterns of the tyrosine-based signal motifs. While the human IFGP members appear to be B-cell antigens, the mouse genes have a broader tissue distribution with predominant expression in brain. Sequence comparisons revealed that the IFGP family may be regarded as a phylogenetic link joining the leukocyte FcRs with the rat NK cell-specific gp42 antigen and platelet endothelial cell adhesion molecule-1 (PECAM-1), two mammalian leukocyte receptors whose close relatives were not found previously. It is suggested that FcRs, the IFGP proteins and gp42 have arisen by a series of duplications from a common ancestor receptor comprised of five Ig-like domains. The organization of the human genes shows that the IFGP family evolved through differential gain and loss of exons due to recombination and/or mutation accumulation in the duplicated copies. 相似文献
118.
119.
Genadii B Borovskii Irina V Stupnikova Anna I Antipina Svetlana V Vladimirova Victor K Voinikov 《BMC plant biology》2002,2(1):5-7
Background
Dehydrins are known as Group II late embryogenesis abundant proteins. Their high hydrophilicity and thermostability suggest that they may be structure stabilizers with detergent and chaperone-like properties. They are localised in the nucleus, cytoplasm, and plasma membrane. We have recently found putative dehydrins in the mitochondria of some cereals in response to cold. It is not known whether dehydrin-like proteins accumulate in plant mitochondria in response to stimuli other than cold stress.Results
We have found five putative dehydrins in the mitochondria of winter wheat, rye and maize seedlings. Two of these polypeptides had the same molecular masses in all three species (63 and 52 kD) and were thermostable. Drought, freezing, cold, and exogenous ABA treatment led to higher accumulation of dehydrin-like protein (dlp) 63 kD in the rye and wheat mitochondria. Protein 52 kD was induced by cold adaptation and ABA. Some accumulation of these proteins in the maize mitochondria was found after cold exposition only. The other three proteins appeared to be heat-sensitive and were either slightly induced or not induced at all by all treatments used.Conclusions
We have found that, not only cold, but also drought, freezing and exogenous ABA treatment result in accumulation of the thermostable dehydrins in plant mitochondria. Most cryotolerant species such as wheat and rye accumulate more heat-stable dehydrins than cryosensitive species such as maize. It has been supposed that their function is to stabilize proteins in the membrane or in the matrix. Heat-sensitive putative dehydrins probably are not involved in the stress reaction and adaptation of plants. 相似文献120.
Acute graft-versus-host disease does not require alloantigen expression on host epithelium 总被引:21,自引:0,他引:21
Alloantigen expression on host antigen-presenting cells (APCs) is essential to initiate graft-versus-host disease (GvHD); therefore, alloantigen expression on host target epithelium is also thought to be essential for tissue damage. We tested this hypothesis in mouse models of GvHD using bone-marrow chimeras in which either major histocompatibility complex class I or class II alloantigen was expressed only on APCs. We found that acute GvHD does not require alloantigen expression on host target epithelium and that neutralization of tumor necrosis factor-alpha and interleukin-1 prevents acute GvHD. These results pertain particularly to CD4-mediated GvHD but also apply, at least in part, to CD8-mediated GvHD. These results challenge current paradigms about the antigen specificity of GvHD effector mechanisms and confirm the central roles of both host APCs and inflammatory cytokines in acute GvHD. 相似文献