全文获取类型
收费全文 | 91篇 |
免费 | 5篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 1篇 |
妇产科学 | 1篇 |
基础医学 | 10篇 |
口腔科学 | 2篇 |
临床医学 | 2篇 |
内科学 | 2篇 |
皮肤病学 | 1篇 |
神经病学 | 7篇 |
特种医学 | 3篇 |
外科学 | 1篇 |
综合类 | 5篇 |
预防医学 | 18篇 |
药学 | 32篇 |
中国医学 | 9篇 |
肿瘤学 | 9篇 |
出版年
2021年 | 1篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2013年 | 5篇 |
2012年 | 6篇 |
2011年 | 11篇 |
2010年 | 6篇 |
2009年 | 5篇 |
2008年 | 6篇 |
2007年 | 11篇 |
2006年 | 4篇 |
2005年 | 2篇 |
2004年 | 4篇 |
2003年 | 3篇 |
2002年 | 4篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1987年 | 1篇 |
1984年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有106条查询结果,搜索用时 93 毫秒
101.
McQuistan TJ Simonich MT Pratt MM Pereira CB Hendricks JD Dashwood RH Williams DE Bailey GS 《Food and chemical toxicology》2012,50(2):341-352
Recent pilot studies found natural chlorophyll (Chl) to inhibit carcinogen uptake and tumorigenesis in rodent and fish models, and to alter uptake and biodistribution of trace (14)C-aflatoxin B1 in human volunteers. The present study extends these promising findings, using a dose-dose matrix design to examine Chl-mediated effects on dibenzo(def,p)chrysene (DBC)-induced DNA adduct formation, tumor incidence, tumor multiplicity, and changes in gene regulation in the trout. The dose-dose matrix design employed an initial 12,360 rainbow trout, which were treated with 0-4000ppm dietary Chl along with 0-225ppm DBC for up to 4weeks. Dietary DBC was found to induce dose-responsive changes in gene expression that were abolished by Chl co-treatment, whereas Chl alone had no effect on the same genes. Chl co-treatment provided a dose-responsive reduction in total DBC-DNA adducts without altering relative adduct intensities along the chromatographic profile. In animals receiving DBC alone, liver tumor incidence (as logit) and tumor multiplicity were linear in DBC dose (as log) up to their maximum-effect dose, and declined thereafter. Chl co-treatment substantially inhibited incidence and multiplicity at DBC doses up to their maximum-effect dose. These results show that Chl concentrations encountered in Chl-rich green vegetables can provide substantial cancer chemoprotection, and suggest that they do so by reducing carcinogen bioavailability. However, at DBC doses above the optima, Chl co-treatments failed to inhibit tumor incidence and significantly enhanced multiplicity. This finding questions the human relevance of chemoprevention studies carried out at high carcinogen doses that are not proven to lie within a linear, or at least monotonic, endpoint dose-response range. 相似文献
102.
Prindiville JS Mennigen JA Zamora JM Moon TW Weber JM 《Toxicology and applied pharmacology》2011,251(3):201-208
Gemfibrozil (GEM) is a fibrate drug consistently found in effluents from sewage treatment plants. This study characterizes the pharmacological effects of GEM on the plasma lipoproteins of rainbow trout (Oncorhynchus mykiss). Our goals were to quantify the impact of the drug on: 1) lipid constituents of lipoproteins (phospholipids (PL), triacylglycerol (TAG), and cholesterol), 2) lipoprotein classes (high, low and very low density lipoproteins), and 3) fatty acid composition of lipoproteins. Potential mechanisms of GEM action were investigated by measuring lipoprotein lipase activity (LPL) and the hepatic gene expression of LPL and of the peroxisome proliferator-activated receptor (PPAR) α, β, and γ isoforms. GEM treatment resulted in decreased plasma lipoprotein levels (− 29%) and a reduced size of all lipoprotein classes (lower PL:TAG ratios). However, the increase in HDL-cholesterol elicited by GEM in humans failed to be observed in trout. Therefore, HDL-cholesterol cannot be used to assess the impact of the drug on fish. GEM also modified lipoprotein composition by reducing the abundance of long-chain n−3 fatty acids, thereby potentially reducing the nutritional quality of exposed fish. The relative gene expression of LPL was increased, but the activity of the enzyme was not, and we found no evidence for the activation of PPAR pathways. The depressing effects of GEM on fish lipoproteins demonstrated here may be a concern in view of the widespread presence of fibrates in aquatic environments. Work is needed to test whether exposure to environmental concentrations of these drugs jeopardizes the capacity of fish for reproduction, temperature acclimation or migratory behaviors. 相似文献
103.
The cell adhesion molecule close homologue of L1 (CHL1) is important for apical dendritic projection and laminar positioning of pyramidal neurons in caudal regions of the cerebral cortex. The p21-activated kinase (PAK1–3) subfamily of serine/threonine kinases has also been implicated in regulating cell adhesion, migration, and morphology. Immunofluorescence staining in mouse embryonic brain showed that PAK1–3 was expressed in embryonic cortex and colocalized with CHL1 during neuronal migration and differentiation. To investigate a cooperative function for CHL1 and PAK in pyramidal cell differentiation or migration, a dominant-negative PAK mutant (PAK1 AID) that inhibits PAK1-3 kinase activity while coexpressing a green fluorescent protein (GFP) reporter was electroporated into the lateral ventricles of wild type (WT) and CHL1 null mutant mouse embryos (E14.5), then brain slices were cultured and neurons analyzed for laminar positioning and morphology by confocal microscopy after 3 days in vitro. Expression of PAK1 AID in CHL1 mutant cortex inactivated PAK and caused embryonic cortical neurons to branch profusely in the intermediate zone (IZ) and cortical plate (CP). The number of nodes, terminals and length of leading processes/apical dendrites of CHL1 mutant embryos expressing PAK1 AID increased dramatically, compared to CHL1 mutants without PAK1 AID, or WT embryos with or without PAK1 AID. These findings suggest that CHL1 and PAK1-3 kinase cooperate, most likely in independent pathways, in regulating morphological development of the leading process/apical dendrite of embryonic cortical neurons. 相似文献
104.
M2 muscarinic receptor extracted from Sf9 cells in cholate-NaCl differs from that extracted from porcine sarcolemma. The latter has been shown to exhibit an anomalous pattern in which the capacity for N-[3H]methylscopolamine (NMS) is only 50% of that for [3H]quinuclidinylbenzilate (QNB), yet unlabeled NMS exhibits high affinity for all of the sites labeled by [3H]QNB. The effects can be explained in terms of cooperativity within a receptor that is at least tetravalent [Park PS, Sum CS, Pawagi AB, Wells JW. Cooperativity and oligomeric status of cardiac muscarinic cholinergic receptors. Biochemistry 2002;41:5588-604]. In contrast, M2 receptor extracted from Sf9 membranes exhibited no shortfall in the capacity for [3H]NMS at either 30 or 4 degrees C, although there was a time-dependent inactivation during incubation with [3H]NMS at 30 degrees C; also, any discrepancies in the affinity of NMS were comparatively small. The level of cholesterol in Sf9 membranes was only 4% of that in sarcolemmal membranes, and it was increased to about 100% by means of cholesterol-methyl-beta-cyclodextrin. M2 receptors extracted from treated Sf9 membranes were stable at 30 and 4 degrees C and resembled those from heart. Cholesterol induced a marked heterogeneity detected in the binding of both radioligands, including a shortfall in the apparent capacity for [3H]NMS, and there were significant discrepancies in the apparent affinity of NMS as estimated directly and via the inhibition of [3H]QNB. The data can be described quantitatively in terms of cooperative effects among six or more interacting sites. Cholesterol therefore appears to promote cooperativity in the binding of antagonists to the M2 muscarinic receptor. 相似文献
105.
106.
Uchida M Yoda N Terahara M Seki K Choi SS Roberts A 《Regulatory toxicology and pharmacology : RTP》2011,60(2):249-261
Propionibacterium freudenreichii ET-3 culture, a cell-free product of whey fermentation using P. freudenreichii ET-3 (7025), has been shown to promote the growth of Bifidobacteria through the action of 1,4-dihydroxy-2-naphthoic acid (DHNA), and therefore, has potential use in the food and supplement industries. Although currently used as a food ingredient in Japan, the safety of this novel ingredient has not been previously evaluated through traditional toxicity testing. Therefore, here we report the results of standard toxicological testing performed on P. freudenreichii ET-3 culture. In a 4-week oral toxicity study, administration of 6000mg/kg body weight/day P. freudenreichii ET-3 culture was without compound-related adverse effects on clinical signs, body weights, food consumption, ophthalmology, hematology, clinical chemistry, urinalysis, organ weights, and gross and microscopic findings in male and female Sprague-Dawley rats. Furthermore, in vitro mutagenicity testing demonstrated that P. freudenreichii ET-3 culture was non-mutagenic in the bacterial reverse mutation assay using a standard battery of bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, and TA1537 and Escherichia coli WP2 uvrA) and non-clastogenic in Chinese hamster lung cells in the mammalian chromosome aberration test. Together, the results of these studies support the safety of P. freudenreichii ET-3 culture for use in foods for human consumption. 相似文献