全文获取类型
收费全文 | 2439篇 |
免费 | 80篇 |
国内免费 | 91篇 |
出版年
2023年 | 13篇 |
2022年 | 30篇 |
2021年 | 25篇 |
2020年 | 35篇 |
2019年 | 45篇 |
2018年 | 58篇 |
2017年 | 37篇 |
2016年 | 64篇 |
2015年 | 71篇 |
2014年 | 128篇 |
2013年 | 223篇 |
2012年 | 102篇 |
2011年 | 150篇 |
2010年 | 98篇 |
2009年 | 103篇 |
2008年 | 120篇 |
2007年 | 134篇 |
2006年 | 144篇 |
2005年 | 136篇 |
2004年 | 120篇 |
2003年 | 126篇 |
2002年 | 89篇 |
2001年 | 56篇 |
2000年 | 31篇 |
1999年 | 48篇 |
1998年 | 34篇 |
1997年 | 39篇 |
1996年 | 33篇 |
1995年 | 35篇 |
1994年 | 40篇 |
1993年 | 23篇 |
1992年 | 22篇 |
1991年 | 21篇 |
1990年 | 30篇 |
1989年 | 13篇 |
1988年 | 14篇 |
1987年 | 20篇 |
1986年 | 10篇 |
1985年 | 9篇 |
1984年 | 15篇 |
1983年 | 13篇 |
1982年 | 21篇 |
1981年 | 9篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1971年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有2610条查询结果,搜索用时 437 毫秒
991.
细胞色素P450超家族4种蛋白质晶体结构比较研究 总被引:2,自引:0,他引:2
通过二级结构特征比较、三维结构比较和疏水图分析阐明了4种P450晶体结构的保守性。尽管4种晶体蛋白的氨基酸序列等同率只有19% ̄26%,但是它们都有相同的13个α螺旋和β1 ̄β4四个片层结构。以P450血红素辅基中卟啉环碳原子作为叠合点叠合4种晶体结构,由叠合结构推导出4种蛋白质基于结构的序列联配。通过计算晶体结构各二线结构Cα原子之间均方根偏差,分类类聚分析法分析,发现P450蛋白三维结构可分为 相似文献
992.
Joanne Zurlo Linda M. Arterburn 《In vitro cellular & developmental biology. Animal》1996,32(4):211-220
Summary An hepatocyte culture system was developed for potential use in toxicological studiesin vitro. Rat hepatocytes were isolated by two-step collagenase perfusion and cultured on Vitrogen-coated Permanox™ dishes in a modified
Chee’s medium containing 1μM dexamethasone and 1% dimethylsulfoxide. The cells remained highly viable for at least 10 d as determined by lactate dehydrogenase
release and total protein levels. Albumin secretion into the medium, as a measure of differentiated function, was maintained
at elevated levels over the course of 10 d in culture. A number of CYP activities were determined by the analysis of testosterone
metabolism in freeze-thawed cells, diazepam metabolism in live cells, and specific assays for CYP 1A1/2, 2B1/2, 2E1, and 3A.
Results of these assays indicated that a wide range of CYP isozymes were maintained, some activities were enhanced under the
conditions of culture and some activities were inducible. Activities of the phase II enzymes, glutathione S-transferase and
UDP-glucuronosyltransferase, and glutathione levels were also maintained in the cultured hepatocytes for at least 6 d. These
results strongly support the use of this hepatocyte culture system forin vitro toxicological studies.
A patent has been filed for the use of the system described herein as anin vitro test kit. 相似文献
993.
The cytochrome P450-containing monooxygenase of Trichosporon cutaneum: Occurrence and properties 总被引:1,自引:0,他引:1
Trichosporon cutaneum metabolizes glucose purely oxidatively and cytochrome P450 was not detected in the reduced CO-difference spectrum of whole cells. However, in the isolated microsomal fraction the corresponding monooxygenase was present as shown by the appearence of cytochrome P450, NADPH-cytochrome c (P450) reductase and cytochrome b5. The absorption maximum of the terminal oxidase in the reduced CO-difference spectrum shifted between 447 and 448 nm. Derepression of biosynthesis of all components was achieved by transition of the cells from carbon- to oxygen-limited growth in continuous culture. The monooxygenase exhibited aminopyrine demethylation activity but not -hydroxylation activity of lauric acid. With respect to the growth limiting nutrient (carbon and oxygen respectively), mitochondrial cytochrome content showed an analogous behavior as cytochrome P450 and cytochrome b5. 相似文献
994.
A one-electron reductive metabolism of 1,2-dibromoethane (DBE) is described that gives rise to a free radical intermediate, which can be stabilized by a spin trapping agent and detected by electron spin resonance spectroscopy. Using rat liver microsomes or isolated hepatocytes from phenobarbitone pretreated animals, under hypoxic conditions, it has been possible to trap a free radical intermediate and identify it by using 13C-DBE. Inhibition experiments have demonstrated that the site of activation is the microsomal drug metabolizing system. 相似文献
995.
The cholesterol content of rat liver plasma membranes was manipulated using either cholesterol-free or cholesterol-enriched liposomes. Removal of cholesterol from the membranes led to a marked increase in 5'-nucleotidase activity. However, increase in cholesterol content failed to exert any significant effect on 5'-nucleotidase activity. Arrhenius plots of the activity of the native enzyme exhibited a break at around 28 degrees C with the activation energy of the reaction less above this temperature than below. In cholesterol-depleted membranes a single break at around 26 degrees C was observed with activation energies greater above this temperature than below it. In cholesterol-enriched membranes Arrhenius plots were linear over the range examined. It is suggested that the lipid environment of the external half of the bilayer only influences 5'-nucleotidase activity in these membranes and that cholesterol exerts controlling effects on both the activity and conformation of the enzyme in native membranes. 相似文献
996.
This study examined various biochemical parameters such as mitochondria and mitochondrial DNA (mtDNA), total heme and cyto P450 content in fresh hepatocytes and dedifferentiated hepatocytes. These parameters were chosen in order to understand the dramatic decrease in drug metabolism in cultured hepatocytes. The data in this study shows a temporal decrease in cytochrome P450, total heme and also a decrease in mitochondria. Also, the ratio of mtDNA content to mitochondrial density was found to increase as hepatocytes underwent dedifferentiation. Stereological analysis of cell preparations provided a measure of mitochondrial density per cell area and mtDNA content was assessed by the use of a specific radiolabelled probe. This study demonstrates that a loss of the organelle which is partially responsible for synthesis of heme correlates with a decrease in cytochrome P450. 相似文献
997.
The activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the hexose monophosphate shunt, was examined in olfactory epithelium, respiratory epithelium, olfactory bulb, and occipital cortex in Fisher 344 rats aged 4 and 24 months. Marked differences in this enzyme were found in olfactory compared to nonolfactory tissues. Olfactory epithelium and olfactory bulb have much greater glucose-6-phosphate dehydrogenase activity than respiratory epithelium and occipital cortex at both ages. Glucose-6-phosphate dehydrogenase remains fairly constant between adulthood and senescence in respiratory epithelium and occipital cortex. However, glucose-6-phosphate dehydrogenase activity decreases during the same time in both of the olfactory tissues examined. Previous studies of changes in this enzyme with aging have shown increases in enzyme activity in some brain regions, but never the decreases that we describe in olfactory tissues. Glucose-6-phosphate dehydrogenase histochemistry revealed intense staining of both the apical layer of olfactory epithelium and of Bowman's glands along with their ducts. Histochemistry of the olfactory bulb showed strongest staining in the nerve and glomerular layers of the bulb. The functional implications of these findings are discussed. 相似文献
998.
T Schulz-Schalge W Heger J Webb M Kastner D Neubert 《Journal of medical primatology》1991,20(7):325-333
The pre- and postnatal development of monooxygenases in the liver and adrenal gland of marmoset monkeys (Callithrix jacchus) was investigated. Cytochrome P450 was detected in the fetal adrenal gland, but aldrin epoxidase, ethoxycoumarin O-deethylase, and ethoxyresorufin O-deethylase activities were below detection limits. Although fetal hepatic cytochrome P450 was not detected, low activities of aldrin epoxidase and ethoxycoumarin O-deethylase, but no ethoxyresorufin O-deethylase, could be detected in fetal liver. These enzymes attained adult marmosets activities when the offspring were approximately 2 months of age. 相似文献
999.
Cryopreservation of isolated rat hepatocytes 总被引:4,自引:0,他引:4
Deborah L. Novicki Grace P. Irons Stephen C. Strom Randy Jirtle George Michalopoulos 《In vitro cellular & developmental biology. Plant》1982,18(4):393-399
Summary Isolated parenchymal hepatocytes from adult rats were frozen in media containing 10% glycerol, 10% dimethylsulfoxide (DMSO),
or 20% DMSO. Three microsome-associated functions were compared in nonfrozen cells and cells frozen in each of the above cryoprotectant
solutions. Freezing in DMSO maintains cytochromes P-450 and b5 and NADPH-cytochrome C reductase at levels nearer to control values than does freezing in glycerol. Cells frozen and subsequently
thawed and cultured for 24 h lose a greater amount of cytochrome P-450 than do nonfrozen cultured cells. The levels of cytochrome
b5 and reductase in frozen-thawed cells remain close to control values. Cell viability (trypan blue dye exclusion and percentage
of attached cells) after freezing is maintained better using DMSO as a cryoprotectant. Dimethylsulfoxide protects the hepatocytes
from freeze-induced damage to the extent that many viable cells attach to collagen-coated petri dishes, survive for at least
24 h, and still maintain significant levels of enzymes of importance to drug and carcinogen metabolism.
This work was supported by Grant CA-30241 from the National Institutes of Health, Bethesda, Maryland. 相似文献
1000.
Purified cytochrome from bovine adrenocortical mitochondria was incorporated into liposomes by the cholate-dilution method utilizing either dialysis or Sephadex gel filtration. Among synthetic phospholipids tested, dioleoylglycerophosphocholine showed the best stability during the incorporation of into liposomes. A maximum amount of heme was incorporated into liposomes at a molar ratio of phospholipid to the cytochrome of approx. 200. When was incorporated into the dioleoylglycerophosphocholine liposomes by the cholate-filtration method, the showed two major populations on the elution pattern of the Sepharose 4B gel filtration, and were seen at a diameter of 200–600 Å and its aggregated forms. When the cytochrome was incorporated into dioleoylglycerophosphocholine liposomes or cholesterol-free adrenocortical mitochondrial liposomes, was less stable than in aqueous solution. Cholesterol or adrenodoxin markedly stabilized the liposomal . Liposomal required cholesterol for its optimum reduction with adrenodoxin, adrenodoxin reductase, and NADPH in the presence of CO. About 70% of the total heme in the dioleoylglycerophosphocholine liposomes was reduced by the enzymatic reduction in the presence of cholesterol, indicating that 70% of the total molecules are exposed to the surface of the outer monolayer. In order to see the location of the heme in membrane, the dioleoylglycerophosphocholine-liposomal was subjected to treatment. This reagent destroyed the liposomal . These results suggest that the heme is located in the proximity of the reacting sites which are exposed to the surface, or located on the vincinity of polar heads of the membrane. 相似文献