全文获取类型
收费全文 | 63篇 |
免费 | 0篇 |
专业分类
儿科学 | 1篇 |
基础医学 | 7篇 |
临床医学 | 5篇 |
内科学 | 1篇 |
皮肤病学 | 3篇 |
神经病学 | 21篇 |
外科学 | 3篇 |
预防医学 | 1篇 |
眼科学 | 1篇 |
药学 | 20篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2015年 | 1篇 |
2012年 | 1篇 |
2011年 | 1篇 |
2010年 | 1篇 |
2009年 | 2篇 |
2008年 | 3篇 |
2007年 | 1篇 |
2006年 | 3篇 |
2005年 | 4篇 |
2004年 | 2篇 |
2003年 | 1篇 |
2002年 | 3篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1995年 | 2篇 |
1992年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1982年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
排序方式: 共有63条查询结果,搜索用时 15 毫秒
1.
A. Enz P. Donatsch R. Nordmann 《Journal of neural transmission (Vienna, Austria : 1996)》1984,60(3-4):225-238
Summary Mesulergine, an 8--aminoergoline, is now proven to be of utility in the clinic as an antiparkinsonian drug. However, the molecule itself showsin vitro andin vivo antidopaminergic properties. Mesulergine is rapidly metabolized into several pharmacologically active DA agonists. The influence of mesulergine on central DA metabolism in rats is dependent on the route of drug administration. It was possible to determine the different metabolites of this drug in plasma as well as in rat striatum. A correlation between the actual present concentration of the parent drug and DAergic metabolites and the net action on striatal DA metabolism was found.It may be concluded that mesulergine itself lacks DAergic activity but occupies DA receptors and is very rapidly metabolized into potent DA agonists. 相似文献
2.
Rose M Dütting E Schröder N Sticht H Brandstätter JH Enz R 《Molecular and cellular neurosciences》2008,37(4):808-819
Phosphorylation and dephosphorylation of neurotransmitter receptors represent an important mechanism to regulate synaptic signal transduction. Here, we identified PNUTS, a targeting subunit of protein phosphatase 1 (PP1) as a new binding partner of GABAC receptors. In the mammalian retina, PNUTS is co-expressed with GABAC receptors and PP1 in bipolar cells. PNUTS and PP1 were detected in membrane protein preparations of the retina and precipitate with GABAC receptor specific antibodies. Furthermore, PNUTS shuttles from the nucleus to the membrane in cells co-expressing GABAC receptors. We show simultaneous binding of PP1 and GABAC receptors to different domains of PNUTS, demonstrating that PNUTS cross-links PP1 and GABAC receptors. Finally, modeling studies showed that the PP1 docking motif of PNUTS fits into the binding pocket on the enzyme surface, despite a C-terminal adjacent proline. We suggest that PNUTS targets PP1 to synaptic sites, acting as a temporary bridge between the phosphatase and GABAC receptors. 相似文献
3.
Absence of receptor reserve at striatal dopamine receptors regulating cholinergic neuronal activity 总被引:2,自引:0,他引:2
N-propylnorapomorphine (NPA) dose dependently increased rat striatal ACh levels (ED50 = 18 micrograms/kg). After irreversible dopamine (DA) receptor inactivation with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), neither the ED50 nor the slope of the dose-response curve for NPA was altered, whereas the maximal response was reduced to 56% of control. Analysis of the results yielded a linear relationship between receptor occupancy and response (i.e. no receptor reserve). In contrast, DA autoreceptors display a large receptor reserve for NPA. The results support the hypothesis that a differential receptor reserve at pre- vs. postsynaptic DA receptors in rat striatum accounts for the autoreceptor selectivity of DA agonists. 相似文献
4.
5.
6.
7.
Rivastigmine, a cholinesterase inhibitor, is successfully used for the symptomatic therapy of Alzheimer's disease (AD) in the clinic. The drug has a very low potential for drug-drug interactions, as has been demonstrated within large clinical trials. Memantine, recently approved by the FDA for the treatment of moderate to severe AD, acts as a low affinity, non-competitive NMDA-antagonist, on a completely different neurotransmitter system, the glutamatergic system. Given the different sites of action, the possibility to combine a cholinergic with a glutamatergic intervention as potentially superior AD therapy has recently been proposed. In vitro studies have demonstrated that memantine, when added to reversible AChE inhibitors, such as tacrine, donepezil or galantamine, did not interfere with the inhibitory action of any of these drugs. The results from the present study provide evidence that rivastigmine as a pseudo-irreversible (or slow-reversible) AChE inhibitor shares this property described for reversible inhibitors, since memantine (1-100 microM), irrespective of whether given prior to or after rivastigmine did not influence rivastigmine's AChE inhibition in vitro. A similar observation was also made under in vivo conditions (ex vivo measurements): following a 21 day chronic, oral administration of 6 micromol/kg rivastigmine alone or of a combination of rivastigmine plus memantine (6 micromol/kg p.o. of either of the two compounds), an identical degree of AChE inhibition was observed. The concentrations of rivastigmine, its metabolite NAP 226-90 and memantine were measured in the brain of the same animals. Following an equimolar oral dose (6 micromol/kg) of both compounds, the brain level of memantine exceeded that of rivastigmine + metabolite, by a factor of around 30, when measured 2 h after the final dosing, irrespective of the duration of treatment (acute, for 3 or 21 days). This indicates that neither of the two drugs showed accumulation but also, and more importantly, that memantine does not modulate the prime therapeutic action of rivastigmine (AChE inhibition) in vitro or in vivo. Clinical trials using a combination of both drugs will provide a final proof of whether a combination therapy would lead to an increased efficacy in AD patients. 相似文献
8.
Alzheimer's disease is a neurodegenerative disorder that affects the cholinergic, glutamatergic and monoaminergic systems in the neocortex and hippocampus. Today, the major pharmacological treatment involves the use of acetylcholinesterase inhibitors (AChEIs). In this study, an in situ hybridisation technique (using digoxigenin-labelled cRNA probes) was used to elucidate changes in mRNA expression of the neuronal glutamate transporter, rat excitatory amino carrier 1 (rEAAC1), after treatment with the AChEI rivastigmine. Compared with saline-treated rats, the rats subchronically (3 days) and chronically (21 days), but not acutely, treated with rivastigmine showed a significant increase in rEAAC1 mRNA expression in the hippocampal areas cornu anterior 1 (CA1), CA2, CA3 and dentate gyrus (p < 0.01), but not in the cortical areas. These results provide the first evidence that the glutamatergic system is modulated following acetylcholinesterase inhibition by rivastigmine, a finding, which is likely to be of importance for the clinical effects. 相似文献
9.
Ballard CG Greig NH Guillozet-Bongaarts AL Enz A Darvesh S 《Current Alzheimer research》2005,2(3):307-318
The cholinergic hypothesis of decline in dementia, whereby deficits in learning, memory and behavior are caused, at least in part, by decreased levels of acetylcholine (ACh) in the brain, first emerged more than 20 years ago. The role for acetylcholinesterase (AChE) and its inhibition in this scheme has long been accepted, but findings from preclinical experiments and clinical trials have placed butyrylcholinesterase (BuChE) alongside AChE as an important contributor to the occurrence, symptoms, progression and responses to treatment in dementia. A number of new lines of evidence suggest that both cholinesterase inhibitors (ChEs) may have broader functions in the CNS than previously thought, which relate to both 'classical' esterase activities of the enzymes as well as non-classical actions unrelated to their enzymatic function. Data suggest involvement of the ChEs in modulating glial activation, cerebral blood flow, the amyloid cascade, and tau phosphorylation. It has therefore been speculated that some actions of the ChEs could affect the underlying disease processes in Alzheimer's disease (AD), and that pharmacological manipulation with ChE inhibitors may affect long-term disease progression. Focusing on new findings relating to BuChE, we review recent evidence that has extended knowledge into the roles of ChEs in health, disease and aging. 相似文献
10.