全文获取类型
收费全文 | 145篇 |
免费 | 14篇 |
出版年
2021年 | 3篇 |
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 4篇 |
2014年 | 6篇 |
2013年 | 9篇 |
2012年 | 6篇 |
2011年 | 10篇 |
2010年 | 4篇 |
2009年 | 7篇 |
2008年 | 4篇 |
2007年 | 11篇 |
2006年 | 3篇 |
2005年 | 7篇 |
2004年 | 6篇 |
2003年 | 6篇 |
2002年 | 2篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1971年 | 3篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1964年 | 1篇 |
1961年 | 1篇 |
1960年 | 1篇 |
1955年 | 1篇 |
1945年 | 1篇 |
排序方式: 共有159条查询结果,搜索用时 15 毫秒
91.
92.
93.
Karl J. Okolotowicz Mary Dwyer Emily Smith John R. Cashman 《Journal of biochemical and molecular toxicology》2014,28(1):23-31
A countermeasure that protects the brain from organophosphate toxicity is an unmet need. Few small molecule reactivators that can cross the blood brain barrier and reactivate brain acetyl cholinesterases have been reported. Herein, we describe preclinical investigations of a new class of amidine–oxime reactivator of cholinesterases with improved potency and blood brain barrier permeability. (Z)‐N‐((E)‐1‐(Dimethylamino)‐2‐(hydroxyimino)ethylidene)butan‐1‐aminium chloride, 1 , is zwitterionic at physiological pH but possesses increased oxime nucleophilicity because of the adjacent amidine functionality. The amidine–oximes reported herein were observed to be nontoxic (up to 200 mg/kg in vivo) and are chemically and metabolically stable. The results presented herein show that uncharged amidine–oxime reactivators such as 1 can penetrate the blood brain barrier in animals and protect from the toxicity of nerve agent model compounds. 相似文献
94.
95.
The effect of the administration of the mycotoxins OTA, ZEA and DON alone resp. in combination on animal health and the residue behavior of pigs from 50 – 60 kg living weight over 90 days was investigated in 4 separate studies. Due to its fast metabolisation the administration of 1000 µg DON resp. 250 µg ZEA per kg feed alone or in combination with other mycotoxins does not lead to detectable residues of these mycotoxins in organs and tissues. Therefore these mycotoxins should not be relevant to the consumer.There is an effect of the simultaneous administration of ZEA resp. DON on the metabolisation resp. secretion of OTA. OTA is of relevance from the point of view of residue toxicology. 相似文献
96.
Rakhit R Robertson J Vande Velde C Horne P Ruth DM Griffin J Cleveland DW Cashman NR Chakrabartty A 《Nature medicine》2007,13(6):754-759
Misfolding of Cu/Zn-superoxide dismutase (SOD1) is emerging as a mechanism underlying motor neuron degeneration in individuals with amyotrophic lateral sclerosis (ALS) who carry a mutant SOD1 gene (SOD1 ALS). Here we describe a structure-guided approach to developing an antibody that specifically recognizes monomer-misfolded forms of SOD1. We raised this antibody to an epitope that is normally buried in the SOD1 native homodimer interface. The SOD1 exposed dimer interface (SEDI) antibody recognizes only those SOD1 conformations in which the native dimer is disrupted or misfolded and thereby exposes the hydrophobic dimer interface. Using the SEDI antibody, we established the presence of monomer-misfolded SOD1 in three ALS mouse models, with G37R, G85R and G93A SOD1 mutations, and in a human individual with an A4V SOD1 mutation. Despite ubiquitous expression, misfolded SOD1 was found primarily within degenerating motor neurons. Misfolded SOD1 appeared before the onset of symptoms and decreased at the end stage of the disease, concomitant with motor neuron loss. 相似文献
97.
98.
5,6-Epoxyeicosatrienoic acid stimulates growth hormone release in rat anterior pituitary cells 总被引:1,自引:0,他引:1
J R Cashman 《Life sciences》1989,44(19):1387-1393
The effect of arachidonic acid and some of its metabolites have been examined in rat anterior pituitary cells for their ability to release growth hormone. The cytochrome P-450 metabolite, 5,6-epoxyeicosatrienoic acid is a much more effective growth-hormone releasing agent than 15-hydroxyeicosatetraenoic acid, 15-hydroxyeicosatetraenoic acid methyl ester, 5-hydroxyeicosatetraenoic acid or arachidonic acid. The release of growth hormone is rapid, dose-dependent and reaches an apparent saturation after eight minutes. These studies described herein provide evidence that lipoxygenase and cyclooxygenase products of arachidonic acid are less potent while cytochrome P-450 products are more potent in the release of growth hormone from anterior pituitary cells. 相似文献
99.
Michael B Coulthart Gerard H Jansen Elina Olsen Deborah L Godal Tim Connolly Bernard CK Choi Zheng Wang Neil R Cashman 《BMC neurology》2011,11(1):133
Background
To better characterize the value of cerebrospinal fluid (CSF) proteins as diagnostic markers in a clinical population of subacute encephalopathy patients with relatively low prevalence of sporadic Creutzfeldt-Jakob disease (sCJD), we studied the diagnostic accuracies of several such markers (14-3-3, tau and S100B) in 1000 prospectively and sequentially recruited Canadian patients with clinically suspected sCJD. 相似文献100.
The nutrient requirements and metabolic pathways used by the developing embryo transition from predominantly pyruvate during early cleavage stages to glucose at the blastocyst; however, the complexities involved in the regulation of metabolism at different developmental stages are not clear. The aims of this study were to examine the role of the malate-aspartate shuttle (MAS) in nutrient metabolism pathways in the developing mouse blastocyst and the consequences of impaired metabolism on embryo viability and fetal and placental growth. Eight-cell-stage mouse embryos were cultured in the presence of the MAS inhibitor amino-oxyacetate, with or without pyruvate as an energy substrate in the media. When the MAS was inhibited, the rate of glycolysis and lactate production was significantly elevated and glucose uptake reduced, relative to control cultured embryos in the presence of pyruvate. Despite these changes in embryo metabolism, this did not influence development to the blastocyst stage, but it did reduce the number of inner cell mass and trophectoderm cells. When these embryos were transferred to psuedopregnant females, inhibition of the MAS significantly reduced the proportion of embryos that implanted and developed into fetuses on Day 18 of pregnancy. Finally, fetal growth was reduced while placental weight was maintained, leading to a decreased fetal:placental weight ratio relative to control embryos. These results suggest that impaired metabolism of glucose in the blastocyst via the MAS alters the ability of the embryos to implant and form a pregnancy and leads to reduced fetal weight, likely via altered placental development and function. 相似文献