全文获取类型
收费全文 | 3774篇 |
免费 | 44篇 |
国内免费 | 52篇 |
出版年
2024年 | 2篇 |
2023年 | 10篇 |
2022年 | 19篇 |
2021年 | 17篇 |
2020年 | 24篇 |
2019年 | 34篇 |
2018年 | 23篇 |
2017年 | 21篇 |
2016年 | 20篇 |
2015年 | 78篇 |
2014年 | 234篇 |
2013年 | 255篇 |
2012年 | 361篇 |
2011年 | 575篇 |
2010年 | 546篇 |
2009年 | 133篇 |
2008年 | 138篇 |
2007年 | 156篇 |
2006年 | 154篇 |
2005年 | 130篇 |
2004年 | 129篇 |
2003年 | 136篇 |
2002年 | 90篇 |
2001年 | 43篇 |
2000年 | 60篇 |
1999年 | 75篇 |
1998年 | 68篇 |
1997年 | 51篇 |
1996年 | 48篇 |
1995年 | 46篇 |
1994年 | 35篇 |
1993年 | 27篇 |
1992年 | 20篇 |
1991年 | 16篇 |
1990年 | 20篇 |
1989年 | 15篇 |
1988年 | 7篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 5篇 |
1984年 | 9篇 |
1983年 | 6篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1978年 | 1篇 |
排序方式: 共有3870条查询结果,搜索用时 31 毫秒
151.
Interaction of Axl receptor tyrosine kinase with C1-TEN,a novel C1 domain-containing protein with homology to tensin 总被引:1,自引:0,他引:1
Hafizi S Alindri F Karlsson R Dahlbäck B 《Biochemical and biophysical research communications》2002,299(5):793-800
Axl receptor tyrosine kinase is implicated in several malignancies and is the receptor for the vitamin K-dependent growth factor Gas6. From a yeast two-hybrid screen of protein-protein interactions with the Axl cytoplasmic domain, we detected a previously uncharacterised SH2 domain-containing protein. We cloned two novel splice variants of this protein that give rise to 1409- and 1419-amino acid proteins, differing only in their N-terminal residues and yielding a 150-kDa protein product by in vitro translation. The Axl-interacting C-terminus contains a tandem SH2 and PTB domain combination homologous to the focal adhesion protein tensin. We detected interaction of Axl with both domains in mammalian cells by co-immunoprecipitation and two-hybrid analyses. In addition, the protein possesses an N-terminal putative phorbol ester-binding C1 domain as well as a central tyrosine phosphatase motif. Thus, we have named the protein C1 domain-containing phosphatase and TENsin homologue (C1-TEN). Northern blot analysis of C1-TEN in human tissues revealed highest expression in heart, kidney, and liver. In summary, we have identified a novel multi-domain intracellular protein that interacts with Axl and which may furthermore be involved in other signal transduction pathways. 相似文献
152.
The protein composition of the outer membrane of Gram-negative bacteria consists of about 20 immunochemically distinct proteins, termed outer membrane proteins (OMPs). Apart from their structural role, OMPs have been shown to have other functions, particularly with regard to transport, and have been classified as permeases and porins. Porins, during their interaction with the host, are immunogenic and also directly stimulate several cellular functions. Porins work both as molecules present on the bacterial surface and as molecules released by bacteria. Lipopolysaccharide and OMPs, the major structural macromolecular constituents of the outer membrane, carry out a fundamental role in the pathogenesis of Gram-negative infections. This brief review describes the multiple facets of the biological activities of porins both in vitro and in vivo, particularly focusing on their ability to induce the expression of cytokines and other factors that modulate cellular activities with either pathological or adaptive consequences. This brief discussion will focus on the signal transmission mechanisms induced by bacterial porins. 相似文献
153.
Translocation, processing and secretion of YvaY, a Bacillus subtilis protein of unknown function, were characterised both in B. subtilis and in Escherichia coli. In its natural host B. subtilis, YvaY was transiently synthesised at the end of the exponential growth phase. It was efficiently secreted into the culture supernatant in spite of a calculated membrane spanning domain in the mature part of the protein. In E. coli, despite the high conservation of Sec-dependent transport components, processing of preYvaY was strongly impaired. To uncover which elements of E. coli and B. subtilis translocation systems are responsible for the observed substrate specificity, components of the B. subtilis Sec-system were co-expressed besides yvaY in E. coli. Expression of B. subtilis secA or secYEG genes did not affect processing, but expression of B. subtilis signal peptidase genes significantly enhanced processing of preYvaY in E. coli. While the major signal peptidases SipS or SipT had a strong stimulatory effect on preYvaY processing, the minor signal peptidases SipU, SipV or SipW had a far less stimulatory effect in E. coli. These results reveal that targeting and translocation of preYvaY is mediated by the E. coli Sec proteins but processing of preYvaY is not performed by E. coli signal peptidase LepB. Thus, differences in substrate specificities of E. coli LepB and the B. subtilis Sip proteins provide the bottleneck for export of YvaY in E. coli. Significant slower processing of preYvaY in absence of SecB indicated that SecB mediates targeting of the B. subtilis precursor. 相似文献
154.
Gibberellin (GA) is a classical plant hormone involved in many aspects of plant growth and development. A family of five homologs called the DELLA proteins, comprised of GAI, RGA, RGL1, RGL2 and RGL3, were recently found to act as critical GA signal mediators in Arabidopsis. Reports have shown that GAI and RGA are coupled together to repress stem elongation growth whereas RGL2 is a major negative regulator of seed germination. GA down-regulates DELLA proteins through protein degradation likely via the proteasome pathway. The conserved and functionally important DELLA domain is responsible for protein stability in response to GA. 相似文献
155.
156.
SbHRGP3 encodes an HRGP whose expression is correlated with the cessation of root elongation in soybean. The wound-inducible expression of SbHRGP3 interestingly requires sucrose although wounding alone induces the expression of many HRGP genes. To examine whether sugar serves as a specific signal on the wound-inducible expression or whether sugar is required to provide ATP, we examined SbHRGP3::GUS expression in transgenic tobacco plants. Various oligosaccharides including non-metabolizable sugar induced SbHRGP3::GUS expression in transgenic plants. The inhibitors of photosynthesis and of cellular respiration did not affect the wound-inducible expression of SbHRGP3::GUS. However, the induction was significantly affected by PCMBS, an inhibitor of active apoplastic phloem loading of sucrose, suggesting that SbHRGP3::GUS expression in phloem tissues requires translocated sucrose. We therefore propose that sugar acts as a specific regulatory signal on the wound-inducible expression of SbHRGP3, rather than acting as a simple provider of ATP.Abbreviations ATP Adenosine triphosphate - DCMU 3-(3,4-Dichlorophenyl)-1,1-dimethylurea - DTT Dithiothreitol - HRGP Hydroxyproline-rich glycoprotein - GUS -Glucuronidase - MU 4-Methylumbelliferone - MUG 4-Methylumbelliferyl ß-glucuronide - PCMBS p-Chloromercuribenzenesulphonic acidCommunicated by I.S. Chung 相似文献
157.
Zygotes of the brown alga Fucus distichus (L.) Powell develop polarity prior to the first embryonic cell division and retain a pattern of asymmetric growth during early embryogenesis. In order to identify F. distichus polypeptides secreted during asymmetric cell growth, we used a functional assay in Saccharomyces cerevisiae to screen a cDNA library generated from asymmetrically growing Fucus embryos for sequences encoding polypeptides that function as signal peptides for secretion. We isolated and sequenced 222 plasmids containing Fucus cDNAs encoding signal peptide activity. The cDNA inserts from these plasmids were translated in silico into 244 potential polypeptide sequences, 169 of which are predicted to contain signal peptides. BlastP analysis of the Fucus sequences revealed similarity between many Fucus proteins and cell surface proteins that function in development in other eukaryotes, including epidermal growth factor (EGF)-like repeat-containing proteins, plant leucine-rich repeat (LRR)-receptor kinases, and algal -1, 3-exoglucanase. However, most of the isolated Fucus polypeptides lack similarity to known proteins. The isolation of cDNAs encoding secreted Fucus proteins provides an important step toward characterizing cell surface proteins important for asymmetric organization and growth in fucoid embryos.Abbreviations ECM extracellular matrix - EGF epidermal growth factor - ER endoplasmic reticulum - LRR leucine-rich repeat - SST signal sequence trap - WAK wall-associated kinase 相似文献
158.
de Carvalho MJ Amorim Jesuino RS Daher BS Silva-Pereira I de Freitas SM Soares CM Felipe MS 《Fungal genetics and biology : FG & B》2003,39(3):204-210
Calmodulin (CaM) modulates intracellular calcium signalling and acts on several metabolic pathways and gene expression regulation in many eukaryotic organisms including human fungal pathogens, such as Candida albicans and Histoplasma capsulatum. The temperature-dependent dimorphic fungus Paracoccidioides brasiliensis is the aetiological agent of paracoccidioidomycosis (PCM). The mycelium (M) to yeast (Y) transition has been shown to be essential for establishment of the infection, although the precise molecular mechanisms of dimorphism in P. brasiliensis are still unknown. In this work, several inhibitory drugs of the Ca(2+)/calmodulin signalling pathway were tested to verify the role of this pathway in the cellular differentiation process of P. brasiliensis. EGTA and the drugs calmidazolium (R24571), trifluoperazine (TFP), and W7 were able to inhibit the M-Y transition. We have cloned and characterized the calmodulin gene from P. brasiliensis, which comprises 924 nucleotides and five introns that are in a conserved position among calmodulin genes. 相似文献
159.
160.