全文获取类型
收费全文 | 747篇 |
免费 | 82篇 |
国内免费 | 1篇 |
出版年
2020年 | 5篇 |
2019年 | 8篇 |
2018年 | 12篇 |
2017年 | 10篇 |
2016年 | 8篇 |
2015年 | 21篇 |
2014年 | 18篇 |
2013年 | 36篇 |
2012年 | 39篇 |
2011年 | 29篇 |
2010年 | 20篇 |
2009年 | 28篇 |
2008年 | 29篇 |
2007年 | 23篇 |
2006年 | 23篇 |
2005年 | 26篇 |
2004年 | 15篇 |
2003年 | 16篇 |
2002年 | 22篇 |
2001年 | 19篇 |
2000年 | 22篇 |
1999年 | 23篇 |
1998年 | 23篇 |
1997年 | 14篇 |
1996年 | 13篇 |
1994年 | 8篇 |
1993年 | 11篇 |
1992年 | 9篇 |
1991年 | 19篇 |
1990年 | 24篇 |
1989年 | 11篇 |
1988年 | 9篇 |
1987年 | 13篇 |
1986年 | 19篇 |
1985年 | 15篇 |
1984年 | 13篇 |
1983年 | 13篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1979年 | 17篇 |
1978年 | 7篇 |
1974年 | 6篇 |
1970年 | 4篇 |
1969年 | 5篇 |
1968年 | 9篇 |
1966年 | 7篇 |
1965年 | 4篇 |
1964年 | 5篇 |
1962年 | 5篇 |
1925年 | 5篇 |
排序方式: 共有830条查询结果,搜索用时 477 毫秒
51.
Rasputin, more promiscuous than ever: a review of G3BP 总被引:1,自引:0,他引:1
Irvine K Stirling R Hume D Kennedy D 《The International journal of developmental biology》2004,48(10):1065-1077
52.
Mainland populations of Arctic reindeer and caribou Rangifer tarandus often undergo extensive movements, whereas populations on islands tend to be isolated and sedentary. To characterize the genetic consequences of this difference, levels of genetic diversity and subdivision of Svalbard reindeer (R. t. platyrhynchus) from two adjacent areas on Nordenskjiöldland, Spitsbergen were estimated using data from up to 14 microsatellites. The mean number of alleles per locus in Svalbard reindeer was 2.4 and mean expected heterozygosity per locus was 0.36. The latter value was significantly lower than in Canadian caribou and Norwegian reindeer but higher than in some other cervid species. Large samples of females (n = 743) and small samples of males (n = 38) from two sites ≈ 45 km apart showed genetic subdivision, which could be due to local population fluctuations or limited gene flow. To our knowledge, this is the first study to report significant differentiation at microsatellite loci in Rangifer at such short geographical distances. Neither population showed genetic evidence for recent population bottlenecks when loci unbiased with respect to heterozygosity were analysed. In contrast, false signals of a recent bottleneck were detected when loci upwardly biased with respect to heterozygosity were analysed. Thus, Svalbard reindeer appeared to conform to the paradigm of island populations made genetically depauperate by genetic drift. 相似文献
53.
Regulation of notch signaling by o-linked fucose 总被引:11,自引:0,他引:11
54.
Panin VM Shao L Lei L Moloney DJ Irvine KD Haltiwanger RS 《The Journal of biological chemistry》2002,277(33):29945-29952
O-Fucose has been identified on epidermal growth factor-like (EGF) repeats of Notch, and elongation of O-fucose has been implicated in the modulation of Notch signaling by Fringe. O-Fucose modifications are also predicted to occur on Notch ligands based on the presence of the C(2)XXGG(S/T)C(3) consensus site (where S/T is the modified amino acid) in a number of the EGF repeats of these proteins. Here we establish that both mammalian and Drosophila Notch ligands are modified with O-fucose glycans, demonstrating that the consensus site was useful for making predictions. The presence of O-fucose on Notch ligands raised the question of whether Fringe, an O-fucose specific beta 1,3-N-acetylglucosaminyltransferase, was capable of modifying O-fucose on the ligands. Indeed, O-fucose on mammalian Delta 1 and Jagged1 can be elongated with Manic Fringe in vivo, and Drosophila Delta and Serrate are substrates for Drosophila Fringe in vitro. These results raise the interesting possibility that alteration of O-fucose glycans on Notch ligands could play a role in the mechanism of Fringe action on Notch signaling. As an initial step to begin addressing the role of the O-fucose glycans on Notch ligands in Notch signaling, a number of mutations in predicted O-fucose glycosylation sites on Drosophila Serrate have been generated. Interestingly, analysis of these mutants has revealed that O-fucose modifications occur on some EGF repeats not predicted by the C(2)XXGGS/TC(3) consensus site. A revised, broad consensus site, C(2)X(3-5)S/TC(3) (where X(3-5) are any 3-5 amino acid residues), is proposed. 相似文献
55.
Intracellular post-translational modifications such as phosphorylation and ubiquitylation have been well studied for their roles in regulating diverse signalling pathways, but we are only just beginning to understand how differential glycosylation is used to regulate intercellular signalling. Recent studies make clear that extracellular post-translational modifications, in the form of glycosylation, are essential for the Notch signalling pathway, and that differences in the extent of glycosylation are a significant mechanism by which this pathway is regulated. 相似文献
56.
A polymerase chain reaction (PCR) assay to identify two common abomasal nematodes Marshallagia marshalli and Ostertagia gruehneri of Svalbard reindeer was developed. Species-specific PCR primers were designed from internal transcribed spacer (ITS)-2 sequences of rDNA and validated using morphologically identified adult male and female nematodes. Using the species-specific primers, a 110 bp fragment was amplified from M. marshalli and its minor morph Marshallagia occidentalis and a 149 bp fragment was amplified from Ostertagia gruehneri and its minor morph Ostertagia arctica. No PCR products were amplified from the third rare species, Teladorsagia circumcincta, or DNA from the reindeer host. The assay provides a useful tool to estimate species composition for both sexes in this nematode community. 相似文献
57.
DNA sequences of ITS-1 and ITS-2 of rDNA were determined for 16 individual adult males each of Ostertagia gruehneri and Ostertagia arctica from Svalbard reindeer (Rangifer tarandus platyrhynchus) and Eurasian tundra reindeer (R. t. tarandus). Each ITS was virtually identical in O. gruehneri and O. arctica and the three mixed bases detected were shared by both species. Our results strongly suggest that O. gruehneri and O. arctica are dimorphic males of the same species. 相似文献
58.
Jones DH Morris JB Morgan CP Kondo H Irvine RF Cockcroft S 《The Journal of biological chemistry》2000,275(18):13962-13966
Phosphatidylinositol (PtdIns) 4,5-bisphosphate is involved in many aspects of membrane traffic, but the regulation of its synthesis is only partially understood. Golgi membranes contain PI 4-kinase activity and a pool of phosphatidylinositol phosphate (PIP), which is further increased by ADP-ribosylation factor 1 (ARF1). COS7 cells were transfected with alpha and beta forms of PI 4-kinase, and only membranes from COS7 cells transfected with PI 4-kinase beta increased their content of PIP when incubated with ARF1. PtdIns(4, 5)P(2) content in Golgi membranes was nonexistent but could be increased to a small extent upon adding either cytosol or Type I or Type II PIP kinases. However, when ARF1 was present, PtdIns(4,5)P(2) levels increased dramatically when membranes were incubated in the presence of cytosol or Type I, but not Type II, PIP kinase. To examine whether ARF1 could directly activate Type I PIP 5-kinase, we used an in vitro assay consisting of phosphatidycholine-containing liposomes, ARF1, and PIP 5-kinase. ARF1 increased Type I PIP 5-kinase activity in a guanine nucleotide-dependent manner, identifying this enzyme as a direct effector for ARF1. 相似文献
59.
The spindle checkpoint control mechanism functions to ensure faithful chromosome segregation by delaying cell division until all chromosomes are correctly oriented on the mitotic spindle. Initially identified in budding yeast, several mammalian spindle checkpoint-associated proteins have recently been identified and partially characterized. These proteins associate with all active human centromeres, including neocentromeres, in the early stages of mitosis prior to the commencement of anaphase. We have examined the status of proteins associated with the checkpoint protein complex (BUB1, BUBR1, BUB3, MAD2), the anaphase-promoting complex (Tsg24, p55CDC), and other proteins associated with mitotic checkpoint control (ERK1, 3F3/2 epitope, hZW10), on a human dicentric chromosome. Each of these proteins was found to specifically associate with only the active centromere, suggesting that only active centromeres participate in the spindle checkpoint. This finding complements previous studies on multicentric chromosomes demonstrating specific association of structural and motor-related centromere proteins with active centromeres, and suggests that centromere inactivation is accompanied by loss of all functionally important centromere proteins. 相似文献
60.
Review: formation and properties of amyloid-like fibrils derived from alpha-synuclein and related proteins 总被引:3,自引:0,他引:3
Synucleinsare small proteins that are highly expressed in brain tissue and are localised at presynaptic terminals in neurons. alpha-Synuclein has been identified as a component of intracellular fibrillar protein deposits in several neurodegenerative diseases, and two mutant forms of alpha-synuclein have been associated with autosomal-dominant Parkinson's Disease. A fragment of alpha-synuclein has also been identified as the non-Abeta component of Alzheimer's Disease amyloid. In this review we describe some structural properties of alpha-synuclein and the two mutant forms, as well as alpha-synuclein fragments, with particular emphasis on their ability to form beta-sheet on ageing and aggregate to form amyloid-like fibrils. Differences in the rates of aggregation and morphologies of the fibrils formed by alpha-synuclein and the two mutant proteins are highlighted. Interactions between alpha-synuclein and other proteins, especially those that are components of amyloid or Lewy bodies, are considered. The toxicity of alpha-synuclein and related peptides towards neurons is also discussing in relation to the aetiology of neurodegenerative diseases. 相似文献