全文获取类型
收费全文 | 93篇 |
免费 | 0篇 |
专业分类
系统科学 | 1篇 |
现状及发展 | 15篇 |
研究方法 | 13篇 |
综合类 | 60篇 |
自然研究 | 4篇 |
出版年
2016年 | 1篇 |
2012年 | 2篇 |
2011年 | 10篇 |
2010年 | 2篇 |
2008年 | 2篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 3篇 |
2004年 | 6篇 |
2003年 | 4篇 |
2002年 | 4篇 |
2001年 | 5篇 |
2000年 | 6篇 |
1999年 | 6篇 |
1998年 | 1篇 |
1994年 | 2篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1966年 | 2篇 |
1960年 | 1篇 |
1958年 | 1篇 |
1955年 | 1篇 |
1954年 | 1篇 |
1948年 | 1篇 |
排序方式: 共有93条查询结果,搜索用时 15 毫秒
21.
Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum 总被引:26,自引:0,他引:26
Throughout the latter half of this century, the development and spread of resistance to most front-line antimalarial compounds used in the prevention and treatment of the most severe form of human malaria has given cause for grave clinical concern. Polymorphisms in pfmdr1, the gene encoding the P-glycoprotein homologue 1 (Pgh1) protein of Plasmodium falciparum, have been linked to chloroquine resistance; Pgh1 has also been implicated in resistance to mefloquine and halofantrine. However, conclusive evidence of a direct causal association between pfmdr1 and resistance to these antimalarials has remained elusive, and a single genetic cross has suggested that Pgh1 is not involved in resistance to chloroquine and mefloquine. Here we provide direct proof that mutations in Pgh1 can confer resistance to mefloquine, quinine and halofantrine. The same mutations influence parasite resistance towards chloroquine in a strain-specific manner and the level of sensitivity to the structurally unrelated compound, artemisinin. This has important implications for the development and efficacy of future antimalarial agents. 相似文献
22.
23.
24.
Characterization of ovarian follicular fluids of sheep, pigs and cows using proton nuclear magnetic resonance spectroscopy 总被引:1,自引:0,他引:1
Proton NMR spectra were produced for Graafian follicular fluids obtained by aspiration from sheep, pig and cow ovaries. The following low molecular mass, non-protein-bound metabolites were detected at concentrations exceeding 0.1 mM: acetate, alanine, creatinine/creatine, glycine, D-3-hydroxybutyrate, lactate, valine. Glucose was difficult to quantify and N-acetyl sugars gave a broad resonance at 2.06 ppm, presumably representing side-chains of glycoproteins. Ethanol was detected at up to millimolar concentrations in some specimens, though the physiological significance of this finding was not clear. The concentrations of all metabolites were comparable to those of plasma. These results have therefore shown that NMR spectroscopy is useful for gaining a broad and semiquantitative impression of the more abundant metabolites in the fluids of preovulatory Graafian follicles. 相似文献
25.
R. G. Gosden I. H. Sadler D. Reed R. H. F. Hunter 《Cellular and molecular life sciences : CMLS》1990,46(10):1012-1015
Summary Proton NMR spectra were produced for Graafian follicular fluids obtained by aspiration from sheep, pig and cow ovaries. The following low molecular mass, non-protein-bound metabolites were detected at concentrations exceeding 0.1 mM: acetate, alanine, creatinine/creatine, glycine, D-3-hydroxybutyrate, lactate, valine. Glucose was difficult to quantify and N-acetyl sugars gave a broad resonance at 2.06 ppm, presumably representing side-chains of glycoproteins. Ethanol was detected at up to millimolar concentrations in some specimens, though the physiological significance of this finding was not clear. The concentrations of all metabolites were comparable to those of plasma. These results have therefore shown that NMR spectroscopy is useful for gaining a broad and semiquantitative impression of the more abundant metabolites in the fluids of preovulatory Graafian follicles. 相似文献
26.
27.
28.
29.
Oltersdorf T Elmore SW Shoemaker AR Armstrong RC Augeri DJ Belli BA Bruncko M Deckwerth TL Dinges J Hajduk PJ Joseph MK Kitada S Korsmeyer SJ Kunzer AR Letai A Li C Mitten MJ Nettesheim DG Ng S Nimmer PM O'Connor JM Oleksijew A Petros AM Reed JC Shen W Tahir SK Thompson CB Tomaselli KJ Wang B Wendt MD Zhang H Fesik SW Rosenberg SH 《Nature》2005,435(7042):677-681
Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy. Bcl-X(L) expression correlates with chemo-resistance of tumour cell lines, and reductions in Bcl-2 increase sensitivity to anticancer drugs and enhance in vivo survival. The development of inhibitors of these proteins as potential anti-cancer therapeutics has been previously explored, but obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting a protein-protein interaction. Here, using nuclear magnetic resonance (NMR)-based screening, parallel synthesis and structure-based design, we have discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w, with an affinity two to three orders of magnitude more potent than previously reported compounds. Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumours, and produces cures in a high percentage of the mice. 相似文献
30.
Antiproliferative effect of β-elemene in chemoresistant ovarian carcinoma cells is mediated through arrest of the cell cycle at the G2-M phase 总被引:3,自引:0,他引:3
Li X Wang G Zhao J Ding H Cunningham C Chen F Flynn DC Reed E Li QQ 《Cellular and molecular life sciences : CMLS》2005,62(7-8):894-904
Elemene is a natural antitumor plant drug. However, the effect of elemene on cell growth in ovarian cancer is unknown. In this study, we show that -elemene inhibited the proliferation of cisplatin-resistant human ovarian cancer cells and their parental cells, but had only a marginal effect in human ovary cells, indicating differential inhibitory effects on cell growth between ovarian cancer cells and normal ovary cells. We also demonstrated for the first time that -elemene markedly enhanced cisplatin-induced growth inhibition in resistant cells compared to sensitive cells. In addition, cell cycle analysis revealed a synergistic effect of -elemene and cisplatin on the induction of cell cycle G2-M arrest in our resistant ovarian carcinoma cells. Furthermore, we showed that treatment of these cells with both drugs downregulated cyclin B1 and Cdc2 expression, but elevated the levels of p53, p21waf1/cip1, p27kip1 and Gadd45. Finally, the combination of -elemene and cisplatin was found to increase the phosphorylation of Cdc2 and Cdc25C, which leads to a reduction in Cdc2-cyclin B1 activity. These novel findings suggest that -elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced growth suppression partly through modulating the cell cycle G2 checkpoint and inducing cell cycle G2-M arrest, which lead to blockade of cell cycle progression.Received 19 January 2005; accepted 5 February 2005 相似文献