全文获取类型
收费全文 | 113篇 |
免费 | 25篇 |
专业分类
妇产科学 | 1篇 |
基础医学 | 16篇 |
临床医学 | 6篇 |
内科学 | 32篇 |
皮肤病学 | 1篇 |
神经病学 | 62篇 |
外科学 | 1篇 |
眼科学 | 1篇 |
药学 | 7篇 |
肿瘤学 | 11篇 |
出版年
2023年 | 1篇 |
2020年 | 1篇 |
2018年 | 2篇 |
2016年 | 1篇 |
2015年 | 1篇 |
2014年 | 3篇 |
2013年 | 1篇 |
2012年 | 9篇 |
2011年 | 4篇 |
2010年 | 3篇 |
2009年 | 1篇 |
2008年 | 9篇 |
2007年 | 9篇 |
2006年 | 11篇 |
2005年 | 5篇 |
2004年 | 5篇 |
2003年 | 4篇 |
2002年 | 7篇 |
2001年 | 2篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有138条查询结果,搜索用时 15 毫秒
41.
42.
43.
44.
45.
46.
Diamant S Podoly E Friedler A Ligumsky H Livnah O Soreq H 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(23):8628-8633
In Alzheimer's disease, both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) colocalize with brain fibrils of amyloid-beta (Abeta) peptides, and synaptic AChE-S facilitates fibril formation by association with insoluble Abeta fibrils. Here, we report that human BChE and BSP41, a synthetic peptide derived from the BChE C terminus, inversely associate with the soluble Abeta conformers and delay the onset and decrease the rate of Abeta fibril formation in vitro, at a 1:100 BChE/Abeta molar ratio and in a dose-dependent manner. The corresponding AChE synthetic peptide (ASP)40 peptide, derived from the homologous C terminus of synaptic human (h)AChE-S, failed to significantly affect Abeta fibril formation, attributing the role of enhancing this process to an AChE domain other than the C terminus. Circular dichroism and molecular modeling confirmed that both ASP40 and BChE synthetic peptide (BSP)41 are amphipathic alpha-helices. However, ASP40 shows symmetric amphipathicity, whereas BSP41 presented an aromatic tryptophan residue in the polar side of the C terminus. That this aromatic residue is causally involved in the attenuating effect of BChE was further supported by mutagenesis experiments in which (W8R) BSP41 showed suppressed capacity to attenuate fibril formation. In Alzheimer's disease, BChE may have thus acquired an inverse role to that of AChE by adopting imperfect amphipathic characteristics of its C terminus. 相似文献
47.
48.
In the adult murine hippocampus, dentate gyrus (DG), neurogenesis and neural cell death are thought to affect learning and memory in incompletely understood mechanism(s). Because cholinergic neurotransmission influences both of these functions, we hypothesized that cholinergic signaling, affected by acetylcholinesterase (AChE) activity, expression level, and alternative splicing, may provide a link between these processes. To challenge this hypothesis, we compared DG neurogenesis in transgenic mice overexpressing engineered "synaptic" AChE-S, incapable of acetylcholine (ACh) hydrolysis (TgSin) with strain-matched controls. In control mice, we observed increasing AChE gene expression with progressing neurogenesis. This involved dividing DG neurons expressing proliferating cell nuclear antigen (PCNA) and Tuj1-positive committed neurons compared with neighboring cells. However, TgSin hippocampi with lower hydrolytic AChE activity showed more PCNA-labeled cells than controls. In contrast, TgS mice overexpressing catalytically active AChE-S, with higher than control levels of AChE hydrolytic activity, presented elevated cell labeling by both bromodeoxyuridine and caspase-3, reflecting facilitated survival of newly born neurons as well as increased neural apoptosis. In comparison, overexpression of the stress-induced "readthrough" AChE-R variant in TgR mice resulted in higher hydrolytic activities but unchanged neurogenesis and apoptosis parameters, while all strains presented similar granule cell layer areas, cell density, and neuron numbers. Importantly, this homeostasis was maintained at a cognitive cost: in the hippocampal-dependent socially transmitted food preference task, TgS and TgSin mice showed impaired acquisition and retention, respectively. Our findings suggest that replacement of AChE-S with AChE-R serves to maintain DG homeostasis and associated cognitive tasks, highlighting the role of cholinergic signaling in adult hippocampal neurogenesis and functioning. 相似文献
49.
Cholinesterases are ubiquitous carboxylesterase type B enzymes capable of hydrolyzing the neuro-transmitter acetylcholine which are transiently expressed in multiple germline, embryonic, and tumor cells. The acute poisoning effects of various organophosphorous compounds are generally attributed to their irreversible covalent interaction with cholinesterases and block of their catalytic activities. We have recently found a de novo inheritable amplification of a CHE gene encoding defective butyryl-cholinesterase (acylcholine acyl hydrolase; EC 3.1.1.8) in a family under prolonged exposure to the agricultural organophosphorous insecticide methyl parathion. Further analysis revealed that both the CHE and the ACHE genes, encoding acetylcholinesterase (acetylcholine acetyl hydrolase; EC 3.1.1.7), are amplified in leukemias and platelet disorders and that the tumorogenic expression of these genes in ovarian carcinomas is associated with their frequent coamplification in these tumors. The amplification of CHE and ACHE genes in normal and tumor tissues might be analogous to the well-known amplification of other genes encoding target proteins to toxic compounds. As such, it could provide cells a selection advantage when exposed to organophosphorous poisons. Further, since cholinesterases appear to play developmentally important roles in multiple cell types, the amplification and overexpression of their corresponding genes might affect fertility, be related to the progression of various tumor types, and bear upon the ecological and clinical risks involved with the common use of organophosphorous poisons. 相似文献
50.
Poly(A)-containing messenger RNA from different ages of postnatal rat cerebellum was translated in the reticulocyte lysate system, using [35S]methionine to label newly synthesized polypeptides. Translation products were identified using crossed immunoelectrophoresis and antisera against whole rat plasma and/or specific plasma proteins, followed by autoradiography. It was found that postnatal cerebellar mRNA directs the synthesis of low density lipoprotein (LDL), fibrinogen, transferrin, alpha 1-macroglobulin, alpha 2-macroglobulin and probably also alpha-fetoprotein, albumin and alpha 1-lipoprotein. mRNAs for several other yet undefined plasma proteins were also detected. In general, the synthesis of plasma proteins appeared to decline with cerebellar maturation. X-irradiation or hypothyroidism resulted in selective changes in the levels of mRNA-directed plasma proteins. In the X-irradiated cerebellum these included an increase in the level of mRNA for alpha-fetoprotein and a decrease in the level of mRNA for fibrinogen. In contrast, hypothyroidism decreased cerebellar plasma protein synthesis in general. These observations indicate that plasma proteins are actively produced within the developing rat cerebellum, and that the rate of their synthesis depends on the developmental stage and is influenced by the types of cells present. 相似文献