全文获取类型
收费全文 | 414篇 |
免费 | 27篇 |
出版年
2023年 | 3篇 |
2022年 | 7篇 |
2021年 | 9篇 |
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 10篇 |
2017年 | 4篇 |
2016年 | 16篇 |
2015年 | 23篇 |
2014年 | 29篇 |
2013年 | 27篇 |
2012年 | 47篇 |
2011年 | 32篇 |
2010年 | 17篇 |
2009年 | 21篇 |
2008年 | 22篇 |
2007年 | 25篇 |
2006年 | 30篇 |
2005年 | 22篇 |
2004年 | 17篇 |
2003年 | 17篇 |
2002年 | 11篇 |
2001年 | 2篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1964年 | 1篇 |
排序方式: 共有441条查询结果,搜索用时 15 毫秒
71.
72.
73.
Interleukin (IL)-18 bioactivity and dsRNA sensing by receptors of innate immunity are key components of anti-viral host defense. Despite extensive data on signal transduction activated by both pathways knowledge on cross-communication is incomplete. By using human PBMC and predendritic KG1 cells, as prototypic IL-18-responsive cellular models, we sought to assess cytokine production under the influence of IL-18 and the dsRNA-mimetic poly (I:C). Here, we report on potent synergy between both mediators concerning pro-inflammatory IFNγ and TNFα production. KG1 data revealed that synergistic induction likely relied on TLR3 and was associated with prolonged/increased activation of NF-κB, as detected by IκB analysis and luciferase reporter assays, respectively. Moreover, extended activation of JNK was mediated by IL-18/poly (I:C). Although vital for innate immunity, overwhelming induction of inflammatory cytokines during viral infections poses the threat of serious collateral tissue damage. The stunning synergism inherent to IL-18/dsRNA-induced TNFα/IFNγ detected herein may contribute to this pathological phenomenon. 相似文献
74.
The identification of areas of endemism is essential in building an area classification, but plays little role in how natural areas are discovered. Rather area monophyly, derived from cladistics, is essential in the discovery of natural area classifications or area taxonomy. We propose Area Taxonomy to be a new sub-discipline of historical biogeography, one that can be revised and debated, and which has its own area nomenclature. Separately to area taxonomy, we outline how natural areas may be discovered by transcribing the concepts of homology and monophyly from biological systematics to historical biogeography, in the form of area homologues, area homologies and area monophyly. 相似文献
75.
Postel A Letzel T Müller F Ehricht R Pourquier P Dauber M Grund C Beer M Harder TC 《Analytical biochemistry》2011,(1):49-31
There is an urgent need for robust subtype-specific serological tests to diagnose influenza A virus infections in poultry and mammals, including humans. Such assays require reliable subtype-specific sources of soluble and authentically folded seroreactive hemagglutinin (HA), one of the integral membrane proteins that determine the serological subtype of influenza viruses. To this purpose, a bigenic pFastBacDual baculovirus transfer vector allowing efficient in vivo biotinylation of soluble HA homo-oligomers expressed via the secretory pathway was developed. An Avi-Tag allowed site-specific biotinylation by a coexpressed genetically modified BirA biotin ligase retained in the endoplasmic reticulum (ER). Highly seroreactive mono-biotinylated HA of recent H5 and H7 influenza A subtypes was secreted from recombinant baculovirus infected High-Five insect cells at levels sufficient to directly load streptavidin-coated enzyme-linked immunosorbent assay (ELISA) matrices, thereby avoiding any purification steps. The recombinant antigens retained authentic antigenicity, including conformation-dependent epitopes involved in hemagglutination inhibition as detected by monoclonal antibodies. This is the first bigenic in vivo biotinylation system established for use in insect cells with secretable recombinant membrane proteins biotinylated by an ER-retained variant of BirA biotin ligase. The proposed technique is expected to significantly increase flexibility in the design of subtype-specific assays, thereby expanding the power of influenza A virus serodiagnosis. 相似文献
76.
Clutch size control in capital breeders such as large waterfowl has been much debated. Some studies have concluded that clutch size in ducks is determined before the start of laying and does not change in response to egg additions or removals. The response, however, may depend on the timing of tests, and experiments may have been too late for females to alter the number of eggs. We here study clutch size responses to predation of first and second eggs in the common eider, using protein fingerprinting of egg albumen to verify that the same female continues laying in the nest after predation. Sixty of 79 females with early egg predation (one or both of the two first eggs) deserted the nest. Among the 19 females that stayed and continued laying, the mean number of eggs produced was 4.4, significantly higher than the 3.7 in non-predated nests. The staying females had similar egg size and clutch initiation date as females that deserted, and their body mass and clutch initiation date was similar to that of females whose clutches were not predated. Even capital-breeding common eiders may therefore be indeterminate layers, as many females in which early eggs are removed lay more eggs than others. A previous study has shown that they can reduce their laying if eggs are added. Our results add to increasing evidence that ducks have more flexible egg production than previously thought. 相似文献
77.
Our understanding of the plasma membrane, once viewed simply as a static barrier, has been revolutionized to encompass a complex, dynamic organelle that integrates the cell with its extracellular environment. Here, we discuss how bidirectional signaling across the plasma membrane is achieved by striking a delicate balance between restriction and propagation of information over different scales of time and space and how underlying dynamic mechanisms give rise to rich, context-dependent signaling responses. In this Review, we show how computer simulations can generate counterintuitive predictions about the spatial organization of these complex processes. 相似文献
78.
Gastropod nacre: structure, properties and growth--biological, chemical and physical basics 总被引:1,自引:0,他引:1
The biogenic polymer/mineral composite nacre is a non-brittle biological ceramic, which self-organizes in aqueous environment and under ambient conditions. It is therefore an important model for new sustainable materials. Its highly controlled structural organization of mineral and organic components at all scales down to the nano- and molecular scales is guided by organic molecules. These molecules then get incorporated into the material to be responsible for properties like fracture mechanics, beauty and corrosion resistance. We report here on structure, properties and growth of columnar (gastropod) nacre with emphasis on the genus Haliotis in contrast to sheet nacre of many bivalves. 相似文献
79.
Quantification of cytosolic interactions identifies Ede1 oligomers as key organizers
of endocytosis
下载免费PDF全文
![点击此处可从《Molecular systems biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dominik Boeke Susanne Trautmann Matthias Meurer Malte Wachsmuth Camilla Godlee Michael Knop Marko Kaksonen 《Molecular systems biology》2014,10(11)
Clathrin-mediated endocytosis is a highly conserved intracellular trafficking pathway that
depends on dynamic protein–protein interactions between up to 60 different proteins. However,
little is known about the spatio-temporal regulation of these interactions. Using fluorescence
(cross)-correlation spectroscopy in yeast, we tested 41 previously reported interactions in
vivo and found 16 to exist in the cytoplasm. These detected cytoplasmic interactions
included the self-interaction of Ede1, homolog of mammalian Eps15. Ede1 is the crucial scaffold for
the organization of the early stages of endocytosis. We show that oligomerization of Ede1 through
its central coiled coil domain is necessary for its localization to the endocytic site and we link
the oligomerization of Ede1 to its function in locally concentrating endocytic adaptors and
organizing the endocytic machinery. Our study sheds light on the importance of the regulation of
protein–protein interactions in the cytoplasm for the assembly of the endocytic machinery
in vivo. 相似文献
80.
Tsang TM Annis DS Kronshage M Fenno JT Usselman LD Mosher DF Krukonis ES 《The Journal of biological chemistry》2012,287(20):16759-16767
The Yersinia pestis adhesin molecule Ail interacts with the extracellular matrix protein fibronectin (Fn) on host cells to facilitate efficient delivery of cytotoxic Yop proteins, a process essential for plague virulence. A number of bacterial pathogens are known to bind to the N-terminal region of Fn, comprising type I Fn (FNI) repeats. Using proteolytically generated Fn fragments and purified recombinant Fn fragments, we demonstrated that Ail binds the centrally located 120-kDa fragment containing type III Fn (FNIII) repeats. A panel of monoclonal antibodies (mAbs) that recognize specific epitopes within the 120-kDa fragment demonstrated that mAb binding to (9)FNIII blocks Ail-mediated bacterial binding to Fn. Epitopes of three mAbs that blocked Ail binding to Fn were mapped to a similar face of (9)FNIII. Antibodies directed against (9)FNIII also inhibited Ail-dependent cell binding activity, thus demonstrating the biological relevance of this Ail binding region on Fn. Bacteria expressing Ail on their surface could also bind a minimal fragment of Fn containing repeats (9-10)FNIII, and this binding was blocked by a mAb specific for (9)FNIII. These data demonstrate that Ail binds to (9)FNIII of Fn and presents Fn to host cells to facilitate cell binding and delivery of Yops (cytotoxins of Y. pestis), a novel interaction, distinct from other bacterial Fn-binding proteins. 相似文献