全文获取类型
收费全文 | 55篇 |
免费 | 5篇 |
出版年
2018年 | 1篇 |
2016年 | 1篇 |
2014年 | 1篇 |
2012年 | 1篇 |
2011年 | 1篇 |
2010年 | 1篇 |
2009年 | 3篇 |
2007年 | 2篇 |
2005年 | 3篇 |
2003年 | 1篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1971年 | 1篇 |
1966年 | 1篇 |
1965年 | 4篇 |
1888年 | 2篇 |
1887年 | 1篇 |
1882年 | 2篇 |
排序方式: 共有60条查询结果,搜索用时 31 毫秒
41.
Pyrazofurin, a pyrimidine nucleoside analogue with antineoplastic activity, inhibits cell proliferation and DNA synthesis in cells by inhibiting uridine 5'-phosphate (UMP) synthase. It has been previously shown in concanavalin A (con A)-stimulated guinea pig lymphocytes (23) that pyrazofurin-inhibited DNA synthesis could be selectively reversed by exogenous uridine (Urd). In this report, we have examined possible mechanisms for the Urd reversal with experiments that determine the ability of exogenous Urd to (a) interfere with either the intracellular transport of pyrazofurin, or the conversion of pyrazofurin to its intracellularly active form, pyrazofurin-5'-phosphate; (b) reverse the pyrazofurin block of [14C]orotic acid incorporation into DNA; and (c) alter the pattern of exogenous [3H]Urd incorporation into DNA-thymine (DNA-Thy) and DNA-cytosine (DNA-Cyt) during pyrazofurin inhibition of pyrimidine de novo biosynthesis. The results of these experiments showed that Urd reversal does not occur through altered pyrazofurin transport or intracellular conversion to pyrazofurin-5'-phosphate, nor does it alter the distribution of [3H]Urd in DNA-Thy and DNA-Cyt. Instead, these findings indicate that the primary mechanism for exogenous Urd reversal of pyrazofurin inhibition of DNA synthesis involves the reversal of pyrazofurin inhibition of UMP synthase, thus restoring orotic acid incorporation into lymphocyte DNA through the pyrimidine de novo pathway. 相似文献
42.
43.
44.
45.
The organization of specific pyrimidine pathways to channel various nucleoside precursors into DNA is poorly understood. We show that concanavalin A-stimulated guinea pig lymphocytes incorporate [3H]dThd, [3H]dCyd, [3H]dUrd, [3H]Cyd and [3H]Urd into DNA-thymines and DNA-cytosines in a highly conserved distribution pattern. DNA-thymines were labeled only by dThd and dUrd, while DNA-cytosines were labeled only by dCyd, Cyd and Urd. The kinetics for the incorporation of the [3H]nucleosides were essentially identical, indicating equivalent abilities to measure DNA synthesis. Pyrazofurin inhibition of the pyrimidine de novo synthetic pathway inhibited cell proliferation and the levels of [3H]nucleoside incorporation by approx. 50%, but did not alter restricted distribution of the [3H]nucleosides among DNA-thymines and DNA-cytosines. These findings indicate the absence of Cyd and dCMP deaminase salvage pathways and suggest either subcellular compartmentalization or differential regulation of ribonucleoside diphosphoreductase which permits reduction of CDP but not UDP. 相似文献
46.
47.
Dafydd R. Owen Margarita Rodriguez-Lens Martin D. Corless Steven M. Gaulier Valerie A. Horne Ross A. Kinloch Graham N. Maw David W. Pearce Huw Rees Tracy J. Ringer Thomas Ryckmans Blanda L.C. Stammen 《Bioorganic & medicinal chemistry letters》2009,19(6):1702-1706
A number of libraries were produced to explore the potential of 2,4-diaminopyridine lead 1. The resulting diaminopyridines proved to be potent and selective δ-opioid receptor agonists. Several rounds of lead optimisation using library chemistry identified compound 17 which went on to show efficacy in an electromyography model of neuropathic pain. The structure–activity relationship of the series against the hERG ion channel proved to be a key selectivity hurdle for the series. 相似文献
48.
Female mink were fed a basal diet supplemented with either 0, 10 100, or 1000 ppm iodine, as potassium iodide, from breeding through lactation. In addition, females were housed in pens sanitized just prior to whelping with 100 or 1000 ppm titratable iodine disinfectant to investigate the effects of these treatments on their reproductive performance. The gestation periods of the iodine-treated mink were shorter than the controls. Kit birth weights were not significantly different from the controls. The average number of kits whelped per female mated in the control group was 5.0. No detrimental effects were observed on litter size or kit survival in the group fed 10 ppm supplemental iodine. Only 2.1 kits per female mated were whelped by the mink fed 100 ppm supplemental iodine and none of the females that received the 1000 ppm supplemental iodine diet whelped. Body weights of kits whelped and nursed by the females that received the 100 ppm supplemental iodine diet were significantly lighter at 4 weeks of age. Kits nursed by females housed in pens sanitized with 100 or 1000 ppm titratable iodine had the greatest biomass at 4 weeks of age. 相似文献
49.
Owen DR Dodd PG Gayton S Greener BS Harbottle GW Mantell SJ Maw GN Osborne SA Rees H Ringer TJ Rodriguez-Lens M Smith GF 《Bioorganic & medicinal chemistry letters》2007,17(2):486-490
A series of novel mGluR1 antagonists have been prepared. Incorporation of fragments derived from weak lead matter into a library led to enhanced potency in a new chemical series. A chemistry driven second library iteration, covering a greatly enhanced area of chemical space, maintained good potency and introduced metabolic stability. 相似文献
50.
Dafydd R. Owen John K. Walker E. Jon Jacobsen John N. Freskos Robert O. Hughes David L. Brown Andrew S. Bell David G. Brown Christopher Phillips Brent V. Mischke John M. Molyneaux Yvette M. Fobian Steve E. Heasley Joseph B. Moon William C. Stallings D. Joseph Rogier David N.A. Fox Michael J. Palmer Tracy Ringer Margarita Rodriquez-Lens Yung Yu 《Bioorganic & medicinal chemistry letters》2009,19(15):4088-4091
A new class of potent and selective PDE5 inhibitors is disclosed. Guided by X-ray crystallographic data, optimization of an HTS lead led to the discovery of a series of 2-aryl, (N8)-alkyl substituted-6-aminosubstituted pyrido[3,2b]pyrazinones which show potent inhibition of the PDE5 enzyme. Synthetic details and some structure–activity relationships are also presented. 相似文献