全文获取类型
收费全文 | 231篇 |
免费 | 8篇 |
专业分类
239篇 |
出版年
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2015年 | 5篇 |
2014年 | 8篇 |
2013年 | 19篇 |
2012年 | 11篇 |
2011年 | 16篇 |
2010年 | 11篇 |
2009年 | 11篇 |
2008年 | 11篇 |
2007年 | 6篇 |
2006年 | 7篇 |
2005年 | 12篇 |
2004年 | 6篇 |
2003年 | 6篇 |
2002年 | 12篇 |
2001年 | 8篇 |
2000年 | 10篇 |
1999年 | 9篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1964年 | 1篇 |
1960年 | 1篇 |
1950年 | 1篇 |
1935年 | 1篇 |
1925年 | 1篇 |
1922年 | 1篇 |
1917年 | 1篇 |
1916年 | 1篇 |
1915年 | 1篇 |
1902年 | 1篇 |
1882年 | 2篇 |
排序方式: 共有239条查询结果,搜索用时 15 毫秒
151.
Increased T cell autoreactivity in the absence of CD40-CD40 ligand interactions: a role of CD40 in regulatory T cell development 总被引:15,自引:0,他引:15
Kumanogoh A Wang X Lee I Watanabe C Kamanaka M Shi W Yoshida K Sato T Habu S Itoh M Sakaguchi N Sakaguchi S Kikutani H 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(1):353-360
Mutations in the CD40 ligand (CD40L) gene lead to X-linked immunodeficiency with hyper-IgM, which is often associated with autoimmune diseases. To determine the contribution of defective CD40-CD40L interactions to T cell autoreactivity, we reconstituted CD40-CD40L interactions by transferring T cells from CD40-deficient mice to syngenic athymic nude mice and assessed autoimmunity. T cells from CD40-deficient mice triggered autoimmune diseases accompanied with elevations of various autoantibodies, while those from wild-type mice did not. In CD40-deficient mice, the CD25(+) CD45RB(low) CD4(+) subpopulation which regulates T cell autoreactivity was markedly reduced. CD40-deficient APCs failed to induce T regulatory cells 1 producing high levels of an inhibitory cytokine, IL-10 in vitro. Furthermore, autoimmune development was inhibited when T cells from CD40-deficient mice were cotransferred with CD45RB(low) CD4(+) T cells from wild-type mice or with T regulatory cells 1 induced on CD40-expressing APCs. Collectively, our results indicate that CD40-CD40L interactions contribute to negative regulation of T cell autoreactivity and that defective interactions can lead to autoimmunity. 相似文献
152.
Extracellular functions of galectin-3 总被引:14,自引:0,他引:14
Galectin-3 has been suspected of modulating cell to extracellular matrix interactions in a novel fashion ever since it was first described. However, the rapid accumulation of research data in just the last 8 years alone has completely changed our perspective of this multifunctional protein. Its chimeric nature (consists of carbohydrate recognition and collagen like domains) somehow makes it suited to interact with a plethora of interesting extracellular matrix proteins some of which might enable it to cross the plasma membrane despite its lack of appropriate signal peptides. It is now becoming established as a mediator of signal transduction events on the cell surface as well as a mediator of a variety of extra-cellular processes such as kidney development, angiogenesis, neuronal functions, tumor metastasis, autoimmune disorders, endocytosis and possibly exocytosis. Nevertheless, it still retains its unique position as a mediator/modulator of cell to extracellular matrix adhesive interactions. Cells, particularly epithelial cells which lack galectin-3 expression, interact poorly with their extracellular matrices. In some of these processes, it functions as a matricellular protein, displaying both pro- and anti-adhesive properties. 相似文献
153.
Kundranda MN Ray S Saria M Friedman D Matrisian LM Lukyanov P Ochieng J 《Biochimica et biophysica acta》2004,1693(2):111-123
Fetuin-A is a major constituent of the fetal bovine serum used extensively in cell culture media. We hereby present data demonstrating that breast carcinoma cells can adhere to immobilized fetuin-A in a calcium-dependent fashion. Interestingly, the cells can also divide and attain confluency under these conditions. Using a proteomic approach, we have identified annexin-II and -VI as the putative cell surface receptors for fetuin-A in the presence of Ca2+ ions. Biotinylation of cell surface proteins followed by immunoprecipitation revealed that annexin-VI was expressed on the extracytoplasmic surface of the cell membranes. Finally, to demonstrate that annexin-II and -VI were the adhesive receptors for fetuin-A, siRNA knockdown of expression of the annexins significantly reduced the calcium-mediated adhesion. Interestingly, we demonstrated that the tumor cells could also adhere to immobilized fetuin-A in the presence of magnesium ions, and that this adhesion was most likely mediated by integrins because neutralizing antibodies against beta1 integrins substantially reduced the adhesion. Our studies suggest that the expression of annexin-II and -VI and possibly other members of the family mediate novel adhesion and signaling mechanisms in tumor cells. 相似文献
154.
Barnor JS Endo Y Habu Y Miyano-Kurosaki N Kitano M Yamamoto H Takaku H 《Bioorganic & medicinal chemistry letters》2004,14(19):4941-4944
We examined the suppressive effect of HIV-1 RNA gene cleavage on HIV-1 expression, using the catalytic RNA subunit RNase P and the 3'-half tRNA(Try) [external guide sequence (EGS)] in cultured cells. HIV-1 expression was inhibited by the tRNA(met)-EGS-U5 and U6-EGS-U5 from the tRNA(met) and U6 promoters, respectively. There was no difference in the inhibitory effects on HIV-1 expression between the tRNA(met) and U6 promoters. 相似文献
155.
Molecular mapping of a fertility restorer gene for Owen cytoplasmic male sterility in sugar beet 总被引:2,自引:0,他引:2
Hagihara E Itchoda N Habu Y Iida S Mikami T Kubo T 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,111(2):250-255
We report here the molecular mapping of a fertility restorer gene (named Rf1) for Owen cytoplasmic male sterility in sugar beet. Eight AFLP and two RAPD markers, tightly linked to the Rf1 locus, were identified using bulked segregant analysis. Three AFLP markers, mAFEM972, mAFEM976 and mAFEM985, were found to co-segregate with the Rf1 allele in our mapping populations. With the help of RFLP markers, previously mapped on the sugar beet genome, we showed that Rf1 is positioned in the terminal region of linkage group Kiel III/Koeln IV. This map location agrees well with that found for the restorer gene X, which suggests that the Rf1 locus corresponds to the X locus. The availability of the molecular markers will facilitate the selection of maintainer–pollinator lines in breeding program and provide the foundation for map-based cloning of the Rf1 gene. 相似文献
156.
Yoshiki Habu Yoichi Sakata Kazuhiro Fukasawa Takeshi Ohno 《Plant molecular biology》1993,23(6):1139-1150
Winged bean Kunitz chymotrypsin inhibitor (WCI) accumulates abundantly in seeds and tuberous roots of winged bean plant. In seeds, the WCI mRNA is observed transiently during seed maturation period. The WCI is encoded by a multigene family and the major WCI (WCI-3) is encoded by two nearly identical genes (WCI-3a and WCI-3b genes), in which nucleotide sequences in the 1.1 kb 5 flanking regions are about 99% homologous to each other and the transcribed regions are completely identical. Here we report the detection of two types of nuclear proteins which bind to the multiple sites in the 5 upstream region of the WCI-3a gene. One of the proteins, band 1-forming protein, also bound to cauliflower mosaic virus 35S (CaMV35S) promoter, but another protein, band 3-forming protein, did not. DNaseI footprinting analysis showed that these proteins bound to AT-rich upstream regions in the WCI-3a gene. Addition of poly(dA-dT)-poly(dA-dT) to the binding reaction inhibited the formation of the retarded bands, while poly(dI-dC)-poly(dI-dC) did not. In various organs and throughout seed maturation period, proteins with invariable binding specificities were detected, and these binding proteins met some operational criteria for high-mobility-group (HMG) proteins. These results suggest that leguminous seed AT-binding proteins reported on several seed storage protein genes may be HMG-like proteins which are present ubiquitously in plant organs.deceased on September 15, 1992 相似文献
157.
158.
159.
Boisclair MD McClure C Josiah S Glass S Bottomley S Kamerkar S Hemmilä I 《Journal of biomolecular screening》2000,5(5):319-328
An assay based on fluorescence resonance energy transfer (FRET) has been developed to screen for ubiquitination inhibitors. The assay measures the transfer of ubiquitin from Ubc4 to HECT protein Rsc 1083. Secondary reagents (streptavidin and antibody to glutathione-S-transferase [GST]), pre-labeled with fluorophores (europium chelate, Eu(3+), and allophycocyanin [APC]), are noncovalently attached via tags (biotin and GST) to the reactants (ubiquitin and Rsc). When Rsc is ubiquitinated, Eu(3+) and APC are brought into close proximity, permitting energy transfer between the two fluorescent labels. FRET was measured as time-resolved fluorescence at the emission wavelength of APC, almost entirely free of nonspecific fluorescence from Eu(3+) and APC. The FRET assay generated a lower ratio of signal to background (8 vs. 31) than an assay for the same ubiquitination step that was developed as a dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA). However, compared to the DELFIA method, use of FRET resulted in higher precision (4% vs. 11% intraplate coefficient of variation). Quenching of fluorescence was minimal when compounds were screened at 10 microg/ml using FRET. Employing a quick and simple homogeneous method, the FRET assay for ubiquitin transfer is ideally suited for high throughput screening. 相似文献
160.
Role of Na+-K+-Cl- cotransport and Na+/Ca2+ exchange in mitochondrial dysfunction in astrocytes following in vitro ischemia 总被引:2,自引:0,他引:2
Kintner DB Luo J Gerdts J Ballard AJ Shull GE Sun D 《American journal of physiology. Cell physiology》2007,292(3):C1113-C1122
Na+-K+-Cl cotransporter isoform 1 (NKCC1) and reverse mode operation of the Na+/Ca2+ exchanger (NCX) contribute to intracellular Na+ and Ca2+ overload in astrocytes following oxygen-glucose deprivation (OGD) and reoxygenation (REOX). Here, we further investigated whether NKCC1 and NCX play a role in mitochondrial Ca2+ (Cam2+) overload and dysfunction. OGD/REOX caused a doubling of mitochondrial-releasable Ca2+ (P < 0.05). When NKCC1 was inhibited with bumetanide, the mitochondrial-releasable Ca2+ was reduced by 42% (P < 0.05). Genetic ablation of NKCC1 also reduced Cam2+ accumulation. Moreover, OGD/REOX in NKCC1+/+ astrocytes caused dissipation of the mitochondrial membrane potential (m) to 42 ± 3% of controls. In contrast, when NKCC1 was inhibited with bumetanide, depolarization of m was attenuated significantly (66 ± 10% of controls, P < 0.05). Cells were also subjected to severe in vitro hypoxia by superfusion with a hypoxic, acidic, ion-shifted Ringer buffer (HAIR). HAIR/REOX triggered a secondary, sustained rise in intracellular Ca2+ that was attenuated by reversal NCX inhibitor KB-R7943. The hypoxia-mediated increase in Cam2+ was accompanied by loss of m and cytochrome c release in NKCC1+/+ astrocytes. Bumetanide or genetic ablation of NKCC1 attenuated mitochondrial dysfunction and astrocyte death following ischemia. Our study suggests that NKCC1 acting in concert with NCX causes a perturbation of Cam2+ homeostasis and mitochondrial dysfunction and cell death following in vitro ischemia. intracellular calcium ion; mitochondrial membrane potential; sodium ion influx; bumetanide; cytochrome c; glial cell death 相似文献