全文获取类型
收费全文 | 480篇 |
免费 | 20篇 |
出版年
2022年 | 3篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 12篇 |
2018年 | 9篇 |
2017年 | 7篇 |
2016年 | 13篇 |
2015年 | 20篇 |
2014年 | 19篇 |
2013年 | 24篇 |
2012年 | 45篇 |
2011年 | 40篇 |
2010年 | 20篇 |
2009年 | 36篇 |
2008年 | 35篇 |
2007年 | 31篇 |
2006年 | 32篇 |
2005年 | 23篇 |
2004年 | 28篇 |
2003年 | 16篇 |
2002年 | 11篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 5篇 |
1998年 | 9篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1974年 | 2篇 |
1970年 | 1篇 |
排序方式: 共有500条查询结果,搜索用时 15 毫秒
31.
Zanin-Zhorov A Tal-Lapidot G Cahalon L Cohen-Sfady M Pevsner-Fischer M Lider O Cohen IR 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(1):41-44
LPS, a molecule produced by Gram-negative bacteria, is known to activate both innate immune cells such as macrophages and adaptive immune B cells via TLR4 signaling. Although TLR4 is also expressed on T cells, LPS was observed not to affect T cell proliferation or cytokine secretion. We now report, however, that LPS can induce human T cells to adhere to fibronectin via TLR4 signaling. This response to LPS was confirmed in mouse T cells; functional TLR4 and MyD88 were required, but T cells from TLR2 knockout mice could respond to LPS. The human T cell response to LPS depended on protein kinase C signaling and involved the phosphorylation of the proline-rich tyrosine kinase (Pyk-2) and p38. LPS also up-regulated the T cell expression of suppressor of cytokine signaling 3, which led to inhibition of T cell chemotaxis toward the chemokine stromal cell-derived factor 1alpha (CXCL12). Thus, LPS, through TLR4 signaling, can affect T cell behavior in inflammation. 相似文献
32.
Receptor-mediated regulation of tomosyn-syntaxin 1A interactions in bovine adrenal chromaffin cells 总被引:1,自引:0,他引:1
Gladycheva SE Lam AD Liu J D'Andrea-Merrins M Yizhar O Lentz SI Ashery U Ernst SA Stuenkel EL 《The Journal of biological chemistry》2007,282(31):22887-22899
Tomosyn, a soluble R-SNARE protein identified as a binding partner of the Q-SNARE syntaxin 1A, is thought to be critical in setting the level of fusion-competent SNARE complexes for neurosecretion. To date, there has been no direct evaluation of the dynamics in which tomosyn transits through tomosyn-SNARE complexes or of the extent to which tomosyn-SNARE complexes are regulated by secretory demand. Here, we employed biochemical and optical approaches to characterize the dynamic properties of tomosyn-syntaxin 1A complexes in live adrenal chromaffin cells. We demonstrate that secretagogue stimulation results in the rapid translocation of tomosyn from the cytosol to plasma membrane regions and that this translocation is associated with an increase in the tomosyn-syntaxin 1A interaction, including increased cycling of tomosyn into tomosyn-SNARE complexes. The secretagogue-induced interaction was strongly reduced by pharmacological inhibition of the Rho-associated coiled-coil forming kinase, a result consistent with findings demonstrating secretagogue-induced activation of RhoA. Stimulation of chromaffin cells with lysophosphatidic acid, a nonsecretory stimulus that strongly activates RhoA, resulted in effects on tomosyn similar to that of application of the secretagogue. In PC-12 cells overexpressing tomosyn, secretagogue stimulation in the presence of lysophosphatidic acid resulted in reduced evoked secretory responses, an effect that was eliminated upon inhibition of Rho-associated coiled-coil forming kinase. Moreover, this effect required an intact interaction between tomosyn and syntaxin 1A. Thus, modulation of the tomosyn-syntaxin 1A interaction in response to secretagogue activation is an important mechanism allowing for dynamic regulation of the secretory response. 相似文献
33.
Subcellular localization determines the delicate balance between the anti- and pro-apoptotic activity of Livin 总被引:4,自引:0,他引:4
Nachmias B Lazar I Elmalech M Abed-El-Rahaman I Asshab Y Mandelboim O Perlman R Ben-Yehuda D 《Apoptosis : an international journal on programmed cell death》2007,12(7):1129-1142
Livin is a member of the Inhibitor of Apoptosis Protein family which inhibits apoptosis induced by a variety of stimuli. We
previously identified Livin and demonstrated that following apoptotic stimuli, Livin is cleaved by effector caspases to produce
a truncated form with paradoxical pro-apoptotic activity. In the present study, we reveal that while full-length Livin shows
diffuse cytoplasmic localization, truncated Livin (tLivin) is found in a peri-nuclear distribution with marked localization
to the Golgi apparatus. Using mutation analysis, we identified two domains that are crucial for the pro-apoptotic activity
of tLivin: the N-terminal region of tLivin which is exposed by cleavage, and the RING domain. We demonstrate that, of the
N-terminal sequence, only the first N-terminal glycine residue dictates the peri-nuclear distribution of tLivin. However,
while the perinuclear localization of tLivin is essential, it is not sufficient for tLivin to exert its pro-apoptotic function.
Once tLivin is properly localized, an intact RING domain enables its pro-apoptotic function.
Electronic Supplementary Material Supplementary material is available in the online version of this article at . 相似文献
34.
35.
36.
37.
MOTIVATION: Early and accurate detection of human pathogen infection is critical for treatment and therapeutics. Here we describe pathogen identification using short RNA subtraction and assembly (SRSA), a detection method that overcomes the requirement of prior knowledge and culturing of pathogens, by using degraded small RNA and deep sequencing technology. We prove our approach's efficiency through identification of a combined viral and bacterial infection in human cells. 相似文献
38.
Background
Activity-induced structural remodeling of dendritic spines and glial cells was recently proposed as an important factor in neuroplasticity and suggested to accompany the induction of long-term potentiation (LTP). Although T1 and diffusion MRI have been used to study structural changes resulting from long-term training, the cellular basis of the findings obtained and their relationship to neuroplasticity are poorly understood.Methodology/Principal Finding
Here we used diffusion tensor imaging (DTI) to examine the microstructural manifestations of neuroplasticity in rats that performed a spatial navigation task. We found that DTI can be used to define the selective localization of neuroplasticity induced by different tasks and that this process is age-dependent in cingulate cortex and corpus callosum and age-independent in the dentate gyrus.Conclusion/Significance
We relate the observed DTI changes to the structural plasticity that occurs in astrocytes and discuss the potential of MRI for probing structural neuroplasticity and hence indirectly localizing LTP. 相似文献39.
The cellular arm of the immune response plays a central role in the defense against intracellular pathogens, such as F. tularensis. To date, whole genome immunoinformatic analyses were limited either to relatively small genomes (e.g. viral) or to preselected subsets of proteins in complex pathogens. Here we present, for the first time, an unbiased bacterial global immunoinformatic screen of the 1740 proteins of F. tularensis subs. holarctica (LVS), aiming at identification of immunogenic peptides eliciting a CTL response. The very large number of predicted MHC class I binders (about 100,000, IC(50) of 1000 nM or less) required the design of a strategy for further down selection of CTL candidates. The approach developed focused on mapping clusters rich in overlapping predicted epitopes, and ranking these "hotspot" regions according to the density of putative binding epitopes. Limited by the experimental load, we selected to screen a library of 1240 putative MHC binders derived from 104 top-ranking highly dense clusters. Peptides were tested for their ability to stimulate IFNγ secretion from splenocytes isolated from LVS vaccinated C57BL/6 mice. The majority of the clusters contained one or more CTL responder peptides and altogether 127 novel epitopes were identified, of which 82 are non-redundant. Accordingly, the level of success in identification of positive CTL responders was 17-25 fold higher than that found for a randomly selected library of 500 predicted MHC binders (IC(50) of 500 nM or less). Most proteins (ca. 2/3) harboring the highly dense hotspots are membrane-associated. The approach for enrichment of true positive CTL epitopes described in this study, which allowed for over 50% increase in the dataset of known T-cell epitopes of F. tularensis, could be applied in immunoinformatic analyses of many other complex pathogen genomes. 相似文献
40.
An identical miRNA of the human JC and BK polyoma viruses targets the stress-induced ligand ULBP3 to escape immune elimination 总被引:1,自引:0,他引:1
Bauman Y Nachmani D Vitenshtein A Tsukerman P Drayman N Stern-Ginossar N Lankry D Gruda R Mandelboim O 《Cell host & microbe》2011,9(2):93-102
The human polyoma viruses JCV and BKV establish asymptomatic persistent infection in 65%-90% of humans but can cause severe illness under immunosuppressive conditions. The mechanisms by which these viruses evade immune recognition are unknown. Here we show that a viral miRNA identical in sequence between JCV and BKV targets the stress-induced ligand ULBP3, which is a protein recognized by the killer receptor NKG2D. Consequently, viral miRNA-mediated ULBP3 downregulation results in reduced NKG2D-mediated killing of virus-infected cells by natural killer (NK) cells. Importantly, when the activity of the viral miRNA was inhibited during infection, NK cells killed the infected cells more efficiently. Because NKG2D is also expressed by various T cell subsets, we propose that JCV and BKV use an identical miRNA that targets ULBP3 to escape detection by both the innate and adaptive immune systems, explaining how these viruses remain latent without being eliminated by the immune system. 相似文献