全文获取类型
收费全文 | 518篇 |
免费 | 88篇 |
国内免费 | 7篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 2篇 |
2018年 | 7篇 |
2017年 | 7篇 |
2016年 | 3篇 |
2015年 | 18篇 |
2014年 | 20篇 |
2013年 | 21篇 |
2012年 | 30篇 |
2011年 | 33篇 |
2010年 | 26篇 |
2009年 | 16篇 |
2008年 | 17篇 |
2007年 | 16篇 |
2006年 | 18篇 |
2005年 | 20篇 |
2004年 | 12篇 |
2003年 | 16篇 |
2002年 | 17篇 |
2001年 | 21篇 |
2000年 | 25篇 |
1999年 | 21篇 |
1998年 | 20篇 |
1997年 | 13篇 |
1996年 | 10篇 |
1995年 | 6篇 |
1994年 | 9篇 |
1993年 | 5篇 |
1992年 | 17篇 |
1991年 | 14篇 |
1990年 | 16篇 |
1989年 | 14篇 |
1988年 | 16篇 |
1987年 | 19篇 |
1986年 | 9篇 |
1985年 | 9篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 9篇 |
1979年 | 7篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1936年 | 1篇 |
排序方式: 共有613条查询结果,搜索用时 812 毫秒
41.
Using a yeast two-hybrid screen, human 14-3-3 epsilon protein was found to interact with human calmodulin. In vitro binding assay between human 14-3-3 epsilon protein/peptide and calmodulin was demonstrated by native gel electrophoresis, and the interaction was shown to be calcium dependent. Our results, along with the association of the 14-3-3 epsilon protein with other signaling proteins, suggest that the 14-3-3 protein could provide a link between signal transduction and cell proliferation. 相似文献
42.
Kok LD Tsui SK Waye M Liew CC Lee CY Fung KP 《Biochemical and biophysical research communications》1999,255(3):717-721
A novel human fibroblast growth factor (hFGF), which shows 75% sequence homology with fibroblast growth factor-9, was isolated in random sequencing of a human heart cDNA library. The full-length sequence is 928 bp, the encoded protein is composed of 168 amino acid residues, and its pI value and molecular weight were estimated to be 8.13 and 19.1 kDa, respectively. RT-PCR using Marathon human heart cDNA shows that the coding region is approximately 507 bp. Southern hybridization showed a single band which indicates that this is a single copy gene. Northern hybridization done on a human multiple tissues blot showed that the gene is preferentially expressed in human heart, very weakly detectable in human brain and not detectable in 18 other different human tissues. 相似文献
43.
44.
Nucleic acid binding properties of the nucleic acid chaperone domain of hepatitis delta antigen 总被引:3,自引:1,他引:2
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Wang CC Chang TC Lin CW Tsui HL Chu PB Chen BS Huang ZS Wu HN 《Nucleic acids research》2003,31(22):6481-6492
The N terminal region of hepatitis delta antigen (HDAg), referred to here as NdAg, has a nucleic acid chaperone activity that modulates the ribozyme activity of hepatitis delta virus (HDV) RNA and stimulates hammerhead ribozyme catalysis. We characterized the nucleic acid binding properties of NdAg, identified the structural and sequence domains important for nucleic acid binding, and studied the correlation between the nucleic acid binding ability and the nucleic acid chaperone activity. NdAg does not recognize the catalytic core of HDV ribozyme specifically. Instead, NdAg interacts with a variety of nucleic acids and has higher affinities to longer nucleic acids. The studies with RNA homopolymers reveal that the binding site size of NdAg is around nine nucleotides long. The extreme N terminal portion of NdAg, the following coiled-coil domain and the basic amino acid clusters in these regions are important for nucleic acid binding. The nucleic acid–NdAg complex is stabilized largely by electrostatic interactions. The formation of RNA–protein complex appears to be a prerequisite for facilitating hammerhead ribozyme catalysis of NdAg and its derivatives. Mutations that reduce the RNA binding activity or high ionic strength that destabilizes the RNA–protein complex, reduce the nucleic acid chaperone activity of NdAg. 相似文献
45.
Selective formation of Sed5p-containing SNARE complexes is mediated by combinatorial binding interactions
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Sed5p is the only syntaxin family member required for protein transport through the yeast Golgi and it is known to bind up to nine other soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins in vivo. We describe in vitro binding experiments in which we identify ternary and quaternary Sed5p-containing SNARE complexes. The formation of SNARE complexes among these endoplasmic reticulum- and Golgi-localized proteins requires Sed5p and is syntaxin-selective. In addition, Sed5p-containing SNARE complexes form selectively and this selectivity is mediated by Sed5p-containing intermediates that discriminate among subsequent binding partners. Although many of these SNAREs have overlapping distributions in vivo, the SNAREs that form complexes with Sed5p in vitro reflect their functionally distinct locales. Although SNARE-SNARE interactions are promiscuous and a single SNARE protein is often found in more than one complex, both the biochemical as well as genetic analyses reported here suggest that this is not a result of nonselective direct substitution of one SNARE for another. Rather our data are consistent with the existence of multiple (perhaps parallel) trafficking pathways where Sed5p-containing SNARE complexes play overlapping and/or distinct functional roles. 相似文献
46.
Interaction of the heart-specific LIM domain protein, FHL2, with DNA-binding nuclear protein, hNP220 总被引:3,自引:0,他引:3
Ng EK Chan KK Wong CH Tsui SK Ngai SM Lee SM Kotaka M Lee CY Waye MM Fung KP 《Journal of cellular biochemistry》2002,84(3):556-566
Using a yeast two-hybrid library screen, we have identified that the heart specific FHL2 protein, four-and-a-half LIM protein 2, interacted with human DNA-binding nuclear protein, hNP220. Domain studies by the yeast two-hybrid interaction assay revealed that the second LIM domain together with the third and the fourth LIM domains of FHL2 were responsible to the binding with hNP220. Using green fluorescent protein (GFP)-FHL2 and blue fluorescent protein (BFP)-hNP220 fusion proteins co-expressed in the same cell, we demonstrated a direct interaction between FHL2 and hNP220 in individual nucleus by two-fusion Fluorescence Resonance Energy Transfer (FRET) assay. Besides, Western blot analysis using affinity-purified anti-FHL2 antipeptide antibodies confirmed a 32-kDa protein of FHL2 in heart only. Virtually no expression of FHL2 protein was detected in brain, liver, lung, kidney, testis, skeletal muscle, and spleen. Moreover, the expression of FHL2 protein was also detectable in the human diseased heart tissues. Our results imply that FHL2 protein can shuttle between cytoplasm and nucleus and may act as a molecular adapter to form a multicomplex with hNP220 in the nucleus, thus we speculate that FHL2 may be particularly important for heart muscle differentiation and the maintenance of the heart phenotype. 相似文献
47.
We reported previously (Cayabyab, F. S., and Schlichter, L. C. (2002) J. Biol. Chem. 277, 13673-13681) a functional interaction between the ERG-1 K(+) channel and Src tyrosine kinase, which increased the current. We now show that the tyrosine phosphatase, SHP-1, which is present in microglia, is increased after brain damage, and is activated by colony-stimulating factor-1, associates with ERG-1 and regulates the current. Patch clamp recordings from the MLS-9 microglia cells were made with pipette solutions containing a recombinant SHP-1 protein: wild type (SHP-1 wild type (wt)), catalytically active (SHP-1 S6), or the substrate-trapping mutant (SHP-1 Cys --> Ser). SHP-1 wt and SHP-1 S6 proteins decreased the current, an effect that was reversed by the phosphatase inhibitor, pervanadate, whereas SHP-1 Cys --> Ser increased the current. Moreover, transient transfection with cDNA for SHP-1 wt or SHP-1 S6 decreased the ERG current without decreasing the protein level. Tyrosine phosphorylation of ERG-1 was decreased by transfection with SHP-1 wt and increased by SHP-1 Cys --> Ser. The decrease in current by active SHP-1 was partly attributed to changes in the voltage dependence of activation and steady-state conductance, whereas inactivation kinetics and voltage dependence were not affected. Our results show that ERG-1 is a SHP-1 substrate constituting the first report that an ion current is regulated by SHP-1. 相似文献
48.
Smith GA Tsui HW Newell EW Jiang X Zhu XP Tsui FW Schlichter LC 《The Journal of biological chemistry》2002,277(21):18528-18534
49.
Autoimmune islet destruction in spontaneous type 1 diabetes is not beta-cell exclusive 总被引:8,自引:0,他引:8
Winer S Tsui H Lau A Song A Li X Cheung RK Sampson A Afifiyan F Elford A Jackowski G Becker DJ Santamaria P Ohashi P Dosch HM 《Nature medicine》2003,9(2):198-205
Pancreatic islets of Langerhans are enveloped by peri-islet Schwann cells (pSC), which express glial fibrillary acidic protein (GFAP) and S100beta. pSC-autoreactive T- and B-cell responses arise in 3- to 4-week-old diabetes-prone non-obese diabetic (NOD) mice, followed by progressive pSC destruction before detectable beta-cell death. Humans with probable prediabetes generate similar autoreactivities, and autoantibodies in islet-cell autoantibody (lCA) -positive sera co-localize to pSC. Moreover, GFAP-specific NOD T-cell lines transferred pathogenic peri-insulitis to NOD/severe combined immunodeficient (NOD/SCID) mice, and immunotherapy with GFAP or S100beta prevented diabetes. pSC survived in rat insulin promoter Iymphocytic choriomeningitis virus (rip-LCMV) glycoprotein/CD8+ T-cell receptor(gp) double-transgenic mice with virus-induced diabetes, suggesting that pSC death is not an obligate consequence of local inflammation and beta-cell destruction. However, pSC were deleted in spontaneously diabetic NOD mice carrying the CD8+/8.3 T-cell receptor transgene, a T cell receptor commonly expressed in earliest islet infiltrates. Autoimmune targeting of pancreatic nervous system tissue elements seems to be an integral, early part of natural type 1 diabetes. 相似文献
50.
Wu PY Hanlon M Eddins M Tsui C Rogers RS Jensen JP Matunis MJ Weissman AM Weisman AM Weissman AM Wolberger C Wolberger CP Pickart CM 《The EMBO journal》2003,22(19):5241-5250
Ubiquitin (Ub) regulates diverse functions in eukaryotes through its attachment to other proteins. The defining step in this protein modification pathway is the attack of a substrate lysine residue on Ub bound through its C-terminus to the active site cysteine residue of a Ub-conjugating enzyme (E2) or certain Ub ligases (E3s). So far, these E2 and E3 cysteine residues are the only enzyme groups known to participate in the catalysis of conjugation. Here we show that a strictly conserved E2 asparagine residue is critical for catalysis of E2- and E2/RING E3-dependent isopeptide bond formation, but dispensable for upstream and downstream reactions of Ub thiol ester formation. In contrast, the strictly conserved histidine and proline residues immediately upstream of the asparagine are dispensable for catalysis of isopeptide bond formation. We propose that the conserved asparagine side chain stabilizes the oxyanion intermediate formed during lysine attack. The E2 asparagine is the first non-covalent catalytic group to be proposed in any Ub conjugation factor. 相似文献