全文获取类型
收费全文 | 168篇 |
免费 | 12篇 |
专业分类
180篇 |
出版年
2022年 | 3篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 4篇 |
2014年 | 3篇 |
2013年 | 23篇 |
2012年 | 13篇 |
2011年 | 6篇 |
2010年 | 3篇 |
2009年 | 2篇 |
2008年 | 12篇 |
2007年 | 12篇 |
2006年 | 7篇 |
2005年 | 14篇 |
2004年 | 11篇 |
2003年 | 8篇 |
2002年 | 4篇 |
2001年 | 5篇 |
2000年 | 7篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1993年 | 1篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有180条查询结果,搜索用时 0 毫秒
21.
22.
23.
24.
Karslioglu E Kleinberger JW Salim FG Cox AE Takane KK Scott DK Stewart AF 《Molecular endocrinology (Baltimore, Md.)》2011,25(10):1760-1772
Adult human β-cells replicate slowly. Also, despite the abundance of rodent β-cell lines, there are no human β-cell lines for diabetes research or therapy. Prior studies in four commonly studied rodent β-cell lines revealed that all four lines displayed an unusual, but strongly reproducible, cell cycle signature: an increase in seven G(1)/S molecules, i.e. cyclins A, D3, and E, and cdk1, -2, -4, and -6. Here, we explore the upstream mechanism(s) that drive these cell cycle changes. Using biochemical, pharmacological and molecular approaches, we surveyed potential upstream mitogenic signaling pathways in Ins 1 and RIN cells. We used both underexpression and overexpression to assess effects on rat and human β-cell proliferation, survival and cell cycle control. Our results indicate that cMyc is: 1) uniquely up-regulated among other candidates; 2) principally responsible for the increase in the seven G(1)/S molecules; and, 3) largely responsible for proliferation in rat β-cell lines. Importantly, cMyc expression in β-cell lines, although some 5- to 7-fold higher than normal rat β-cells, is far below the levels (75- to 150-fold) previously associated with β-cell death and dedifferentiation. Notably, modest overexpression of cMyc is able to drive proliferation without cell death in normal rat and human β-cells. We conclude that cMyc is an important driver of replication in the two most commonly employed rat β-cell lines. These studies reverse the current paradigm in which cMyc overexpression is inevitably associated with β-cell death and dedifferentiation. The cMyc pathway provides potential approaches, targets, and tools for driving and sustaining human β-cell replication. 相似文献
25.
Tumor necrosis factor as an activator of human granulocytes. Potentiation of the metabolisms triggered by the Ca2+-mobilizing agonists 总被引:3,自引:0,他引:3
A Yuo S Kitagawa I Suzuki A Urabe T Okabe M Saito F Takaku 《Journal of immunology (Baltimore, Md. : 1950)》1989,142(5):1678-1684
TNF stimulated superoxide (O2-) release directly in human granulocytes in a dose-dependent manner (1 to 1000 U/ml), although its potency was weak. TNF-induced O2- release was inhibited by cAMP agonists or ionomycin, and was not accompanied with an increase in cytoplasmic free Ca2+ [( Ca2+]i) and membrane potential changes (depolarization). These findings indicate that neither Ca2+ mobilization nor membrane depolarization is required for TNF-receptor-mediated cell activation. The pretreatment of human granulocytes with TNF enhanced O2- release and membrane depolarization in parallel stimulated by the receptor-mediated Ca2+-mobilizing agonists (FMLP, Con A, and wheat germ agglutinin) or the Ca2+ ionophore ionomycin, but not by PMA, a direct activator of protein kinase C. The optimal effect was obtained by pretreatment of cells with 100 U/ml TNF for 5 to 10 min at 37 degrees C, although the magnitude of enhancement varied according to the agonists used as subsequent stimuli. TNF did not affect an increase in [Ca2+]i stimulated by the Ca2+-mobilizing agonists, except Con A. Con A-induced increase in [Ca2+]i was enhanced by TNF in a dose-dependent manner. These diverse effects of TNF could be partly explained by the exclusive potentiation by TNF of the metabolic events triggered by an increase in [Ca2+]i. 相似文献
26.
A new nor-sesquiterpene glycoside, isolated from flue-cured tobacco, was identified as rishitin-β-sophoroside. The absolute configuration of the aglycone, rishitin, was identical with that obtained from potato tuber tissue infected by pathogens. 相似文献
27.
Burioka N Takata M Okano Y Ohdo S Fukuoka Y Miyata M Takane H Endo M Suyama H Shimizu E 《Chronobiology international》2005,22(3):585-590
We determined whether human peripheral blood mononuclear cells (PBMCs) could be used to analyze clock genes by studying their mRNA expressions in human bronchial epithelium (BEAS-2B) and PBMCs following stimulation by the glucocorticoid homologue dexamethasone (DEX) in vitro. PBMCs were obtained at 10:00 h from two diurnally active (∼07:00 to 23:00 h) healthy volunteers and were evaluated for hPer1 mRNA expression following DEX stimulation in vitro using real time-PCR analysis. DEX stimulation of human BEAS-2B cells and PBMCs in vitro led to a remarkable increase of hPer1 mRNA. The glucocorticoid rapidly affected the expression of hPer1 mRNA in PBMCs, suggesting that human PBMCs may be a useful surrogate marker for the investigation of drug effects on clock genes. 相似文献
28.
Suzuki Y Claflin J Wang X Lengi A Kikuchi T 《International journal for parasitology》2005,35(1):83-90
We previously reported the requirement of interferon-gamma (IFN-gamma) expression by cells other than T and natural killer (NK) cells in the brain, in addition to T cells, for prevention of toxoplasmic encephalitis following infection with Toxoplasma gondii. In the present study, we analysed the identity of the IFN-gamma-producing non-T, non-NK cells in the brain using infected athymic nude and SCID mice that lack T cells but express IFN-gamma in their brains. Intracellular staining for IFN-gamma followed by flow cytometry revealed that approximately 45-60% of the cells expressing IFN-gamma in their brains were positive for CD11b or F4/80 on their surfaces. Smaller portions of the cells were positive for pan-NK marker. Further smaller portions were positive for CD11c, and these cells were less than 5% of the IFN-gamma-expressing cells in brains of infected SCID mice. In addition to IFN-gamma proteins, large amounts of mRNA for IFN-gamma were detected in CD11b+ cells purified from brains of infected mice, but it was not the case in the cells obtained from uninfected animals. In infected SCID mice depleted of NK cells by treatment with anti-asialo-GM1 antibody, cells expressing IFN-gamma in their brains were all positive for CD11b, and the IFN-gamma-producing cells were detected in both CD45low and CD45high populations. These results suggest that CD11b+ CD45low microglia and CD11b+ CD45high blood-derived macrophages are the major non-T, non-NK cells which express IFN-gamma in the brain of mice infected with T. gondii. 相似文献
29.
Aoki K Uchiyama R Yamauchi S Katayama T Itonori S Sugita M Hada N Yamada-Hada J Takeda T Kumagai H Yamamoto K 《The Journal of biological chemistry》2004,279(31):32028-32034
We found for the first time that Zygomycetes species showed resistance to Aureobasidin A, an antifungal agent. A novel family of neutral glycosphingolipids (GSLs) was found in these fungi and isolated from Mucor hiemalis, which is a typical Zygomycetes species. Their structures were completely determined by compositional sugar, fatty acid, and sphingoid analyses, methylation analysis, matrix-assisted laser desorption ionization time-of-flight/mass spectrometry, and (1)H NMR spectroscopy. They were as follows: Gal beta 1-6Gal beta 1-1Cer (CDS), Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CTS), Gal alpha 1-6Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CTeS), and Gal alpha 1-6Gal alpha 1-6Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CPS). The ceramide moieties of these GSLs consist of 24:0, 25:0, and 26:0 2-hydroxy acids as major fatty acids and 4-hydroxyoctadecasphinganine (phytosphingosine) as the sole sphingoid. However, the glycosylinositolphosphoceramide families that are the major GSLs components in fungi were not detected in Zygomycetes at all. This seems to be the reason that Aureobasidin A is not effective for Zygomycetes as an antifungal agent. Our results indicate that the biosynthetic pathway for GSLs in Zygomycetes is significantly different from those in other fungi and suggest that any inhibitor of this pathway may be effective for mucormycosis, which is a serious pathogenic disease for humans. 相似文献
30.