全文获取类型
收费全文 | 184篇 |
免费 | 1篇 |
国内免费 | 1篇 |
专业分类
基础医学 | 22篇 |
临床医学 | 6篇 |
内科学 | 5篇 |
神经病学 | 73篇 |
特种医学 | 1篇 |
外科学 | 1篇 |
综合类 | 4篇 |
预防医学 | 2篇 |
药学 | 69篇 |
中国医学 | 2篇 |
肿瘤学 | 1篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 1篇 |
2014年 | 1篇 |
2013年 | 6篇 |
2012年 | 7篇 |
2011年 | 6篇 |
2010年 | 7篇 |
2009年 | 10篇 |
2008年 | 5篇 |
2007年 | 4篇 |
2006年 | 5篇 |
2005年 | 3篇 |
2004年 | 2篇 |
2003年 | 3篇 |
2002年 | 6篇 |
2000年 | 5篇 |
1998年 | 3篇 |
1997年 | 7篇 |
1996年 | 7篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 5篇 |
1975年 | 6篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 8篇 |
1970年 | 1篇 |
排序方式: 共有186条查询结果,搜索用时 15 毫秒
1.
Iwao Kadobayashi Masahiko Mori Kunio Tanaka Akiteru Toyoshima Nobukatsu Kato 《Physiology & behavior》1980,25(2):317-320
Small doses (10 and 20 mg/kg) of L-DOPA inhibited the amplitude of the visual evoked response (VER), while large doses (40 and 80 mg/kg) enhanced it. Though low doses (12.5 and 25 mg/kg) of L-5-HTP caused a slight increase in amplitude of the VER, the simultaneous administration of 12.5 mg/kg of L-5-HTP and 10 mg/kg of L-DOPA produced a marked enhancement. The peak latency was prolonged after the injection of any doses of L-DOPA, L-5-HTP, or both. 相似文献
2.
G. Skuza Z. Rogoz G. Quack W. Danysz 《Journal of neural transmission (Vienna, Austria : 1996)》1994,98(1):57-67
Summary Some treatments used for Parkinson's disease attenuate locomotor depression in rats treated with reserpine and -methyl-p-tyrosine. In the present study memantine (2.5, 5.0mg/kg), amantadine (10, 20mg/kg) (both uncompetitive NMDA antagonists), and L-deprenyl (1.0, 5.0 mg/kg; MAO-B inhibitor) were tested for possible synergistic interactions with the dopamine agonists: bromocriptine (2.5, 5.0mg/kg) and L-DOPA (50, 100mg/kg, + benserazide, 100 mg/kg). At higher doses, memantine (10 mg/kg), amantadine (40 mg/kg), bromocriptine (5 and 10mg/kg) and L-DOPA (100, 200mg/kg) but not L-deprenyl (up to 10 mg/kg) produced a pronounced increase in locomotor activity when given alone. The combination of memantine, amantadine and L-deprenyl with bromocriptine did not result in synergism of action and, at best, an additive effect was seen. On the other hand the combination of these agents with L-DOPA produced a pronounced synergistic effect. Hence, the clinical observation that coadministration of L-DOPA with either memantine or amantadine results in enhancement of their action is also reflected in an animal model of Parkinson's disease. Such a combination therapy should allow the use of lower doses of both drugs which may reduce the occurrence of side effects and may also be predicted to have additional benefits related to the neuroprotective properties of memantine, amantadine, and L-deprenyl. 相似文献
3.
T. Brannan A. Prikhojan J. Martínez-Tica M. D. Yahr 《Journal of neural transmission (Vienna, Austria : 1996)》1995,10(2-3):79-89
Summary Utilizing the cerebral microdialysis technique, we have compared in vivo the effects of selective MAO-A, MAO-B, and nonselective MAO inhibitors on striatal extracellular levels of dopamine (DA) and DA metabolites (DOPAC and HVA). The measurements were made in rats both under basal conditions and following L-DOPA administration. Extracellular levels of dopamine were enhanced and DA metabolite levels strongly inhibited both under basal conditions and following L-DOPA administration by pretreatment with the nonselective MAO inhibitor pargyline and the MAO-A selective inhibitors clorgyline and Ro 41-1049. The MAO-B inhibitor deprenyl had no effect on basal DA, HVA, or DOPAC levels. Nervertheless, deprenyl significantly increased DA and decreased DOPAC levels following exogenous L-DOPA administration, a finding compatible with a significant glial metabolism of DA formed from exogenous L-DOPA. We conclude that DA metabolism underbasal conditions is primarily mediated by MAO-A. In contrast, both MAO-A and MAO-B mediate DA formation when L-DOPA is administered exogenously. The efficacy of newer, reversible agents which lack the cheese effect such as Ro 41-1049 are comparable to the irreversible MAO-A inhibitor clorgyline. The possible relevance of these findings for the treatment of Parkinson's disease is discussed. 相似文献
4.
P.A. Caro Aponte C.A. Otálora J.C. Guzmán L.F. Turner J.P. Alcázar E.L. Mayorga 《Neurología (Barcelona, Spain)》2021,36(3):191-200
Parkinson's disease (PD) is characterised by motor alterations, which are commonly treated with L-DOPA. However, long-term L-DOPA use may cause dyskinesia. Although the pathogenic mechanism of L-DOPA-induced dyskinesia is unclear, the condition has been associated with alterations in dopamine receptors, among which D2 receptors (D2R) have received little attention. This study aims to: (i) develop and standardise an experimental model of L-DOPA-induced dyskinesia in rats with hemiparkinsonism; and (ii) evaluate the correlation between D2R expression and presence of abnormal involuntary movements (AIM). We allocated 21 male Wistar rats into 3 groups: intact controls, lesioned rats (with neurotoxin 6-OHDA), and dyskinetic rats (injected with L-DOPA for 19 days). Sensorimotor impairment was assessed with behavioural tests. Dyskinetic rats gradually developed AIMs during the treatment period; front leg AIMs were more severe and locomotor AIMs less severe (P < .05). All AIMs were significantly evident from day 5 and persisted until the last day of injection. D2R density was greater in the striatum and the medial anterior brain of the lesioned and dyskinetic rats than in those of controls. Our results suggest an association between D2R expression and locomotor AIMs. We conclude that RD2 is involved in L-DOPA-induced dyskinesia. 相似文献
5.
Dementia in Parkinson's disease (PDD) and dementia with Lewy bodies (DLB) are characterized by loss of acetylcholine (ACh) from cortical areas. Clinical studies report positive effects of acetylcholine esterase (AChE) inhibitors in PDD and dementia with Lewy bodies. We here report that the number of neurons expressing a cholinergic marker in the medial septum-diagonal band of Broca complex decreases in A30P α-synuclein-expressing mice during aging, paralleled by a lower AChE fiber density in the dentate gyrus and in the hippocampal CA1 field. After inducing dopamine depletion by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), no acute but a delayed loss of cholinergic neurons and AChE-positive fibers was observed, which was attenuated by L-3,4-dihydroxyphenylalanine (DOPA) treatment. Expression of nerve growth factor (NGF) and tyrosine receptor kinase A (TrkA) genes was upregulated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride-treated wild type mice, but not in A30P α-synuclein expressing animals. In contrast, upregulation of sortilin and p75NTR genes was found in the A30P α-synuclein-expressing mice. These results suggest that dopamine deficiency may contribute to the impairment of the septohippocampal system in patients with PDD and that L-3,4-dihydroxyphenylalanine may not only result in symptomatic treatment of the akinetic-rigid syndrome but may also alleviate the degeneration of basal forebrain cholinergic system and the cognitive decline. 相似文献
6.
7.
Ursula Scheffel Christine Steinert Sang Eun Kim Michael D. Ehlers John W. Boja Michael J. Kuhar 《Synapse (New York, N.Y.)》1996,23(2):61-69
[11C]WIN 35,428 (also designated [11C]CFT) is now being used in several positron emission tomography (PET) centers to image dopamine (DA) transporter sites in the mammalian brain. Whether and to what extent in vivo WIN 35,428 binding is influenced by intra- and extrasynaptic dopamine levels are largely unknown. The purpose of the present study was to evaluate the effects of various drugs, known to affect DA levels and release, on the binding of [3H]WIN 35,428 to central DA transporters in the mouse brain. D-Amphetamine, which releases DA from neurons and blocks the DA transporter directly, inhibited striatal [3H]WIN 35,428 binding in dose-dependent manner. Similarly, α-methyl-DL-p-tyrosine, an inhibitor of tyrosine hydroxylase, blocked [3H]WIN 35,428 binding, possibly via competitive inhibition by the metabolite p-hydroxyamphetamine. Specific binding of [3H]WIN 35,428 was insensitive to changes in synaptic DA levels caused by pretreatment of the animals with high doses of D2 receptor agonists (apomorphine, bromocriptine), antagonists (haloperidol) or the inhibitor of dopaminergic neuron firing γ-butyrolactone (GBL). High doses (>50 mg/kg) of L-DOPA (in combination with benserazide), however, reduced [3H]WIN 35,428 binding significantly, yet for a relatively short time (approximately 2.5 h). Chronic treatment with L-deprenyl elicited no changes in in vivo [3H]WIN 35,428 accumulation in the striatum. Neurotoxic damage of DA neurons caused by administration of high doses of amphetamine was detected in the striatum by a significant reduction in [3H]WIN 35,428 binding 7 days after cessation of amphetamine treatment. Thus, [3H]WIN 35,428 binding was only affected by neurotoxic loss of neurons, by administration of uptake inhibitors, or by some treatments which significantly elevate DA levels. Compounds which inhibit DA release or deplete DA acutely do not increase [3H]WIN 35,428 binding, suggesting that normal or “resting” levels of DA are not sufficient to alter [3H]WIN 35,428 binding in vivo. These findings are important for our understanding of the function and regulation of the DA transporter, as well as the in vivo binding of the radioligand [3H/11C]WIN 35,428. Moreover, they will be important for the interpretation of PET studies in which [11C]WIN 35,428 is used to assess the integrity of dopaminergic neurons. © 1996 Wiley-Liss, Inc. 相似文献
8.
The present work studied the transport of L-DOPA in cultured rat and mouse astrocytes. Results indicated that the uptake of L-[14C]DOPA in both rat and mouse astrocytes was Na+ independent and temperature sensitive. It was mediated by a carrier-mediated mechanism with Km values of 36 and 60.3 μM, and Vmax values of 2.4 and 1.9 nmol/min/mg protein for rat and mouse cells, respectively. L-DOPA uptake was potently inhibited by aromatic or branched-chain amino acids. Interestingly, the release of intracellular L-[14C]DOPA was also trans stimulated by competitors that affect L-DOPA uptake. The 14C recovered in the 2-min uptake process was identified as L-[14C]DOPA. However, [14C]dopamine (DA) was also detected in both rat and mouse astrocytes after 30 min L-DOPA incubation, indicating the existence of aromatic L-amino acid decarboxylase (AADC). Taken together, L-DOPA was uphill transported into rat and mouse astrocytes by a Na+-independent exchanger with preference for aromatic and branched-chain amino acids. Rat astrocytes possessed higher affinity for L-DOPA uptake than mouse astrocytes. Both cells synthesized DA from exogenous L-DOPA. Thus, astrocytes serve not only as a temporary storage site for L-DOPA but also as a DA-producing machinery. These results may be of particular importance to parkinsonian patients under L-DOPA medication. © 1996 Wiley-Liss, Inc. 相似文献
9.
D. E. Dluzen F. T. Kratko Jr. 《Journal of neural transmission (Vienna, Austria : 1996)》1992,89(3):197-207
Summary In the present experiment we tested the effects of L-DOPA upon dopamine (DA) efflux in vitro from superfused corpus striatal tissue fragments in medium containing reserpine. The purposes of this experiment were first, to evaluate the effects of differing infusion modes of L-DOPA upon DA efflux under conditions in which DA storage capacity has been diminished, and second, to compare this L-DOPA stimulated DA efflux with that of other putative DA secretagogues such as amphetamine and postassium. No differences were obtained in stimulated DA efflux between superfusions performed in the presence or absence of reserpine (10 M) in the medium when L-DOPA (5 M) was infused in a continuous (70 minute) mode during the superfusion. In contrast, a continuous infusion of either amphetamine (10 M) or high potassium (30 mM) resulted in significantly greater stimulated DA efflux in superfusions performed with reserpine in the medium. In addition, when L-DOPA (5 M) was administered for a brief 10-minute infusion period, a significantly greater stimulated DA efflux was obtained with superfusions containing reserpine in the medium. These results suggest that the mode of L-DOPA infusion may be an important factor in regulating DA release under conditions of diminished DA storage capacity. 相似文献
10.
PNU-96391A is a weak dopamine (DA) D(2) receptor antagonist with behavioral stabilizing properties. Previous experiments revealed that PNU-96391A antagonizes the expression of L-DOPA induced behavioral sensitization (dyskinesias) in lesioned primates without inducing akinesia or reducing the anti-Parkinsonian efficacy of L-DOPA. This study evaluated the ability of PNU-96391A to block the development of DA agonist-induced behavioral sensitization in rats with unilateral 6-OH-DA lesions of the median forebrain bundle. Repeated twice daily treatment with L-DOPA and the decarboxylase inhibitor benserazide (15 and 5 mg/kg, IP, respectively), or quinpirole (D(2)/D(3) agonist, 0.1 mg/kg, SC) increased the contralateral rotations measured on day 7 and 14 as compared to day 1. PNU-96391A (10-60 mg/kg, SC, bid.) antagonized the development of behavioral sensitization induced by both agonists. The basal activity of L-DOPA was not affected while a reduction of quinpirole-induced rotations was observed after 30-60 mg/kg, SC of PNU-96391A. Neurochemical analyses confirmed >99 % reductions of striatal DA levels, unilaterally. Concomitant treatment with PNU-96391A and L-DOPA did not affect plasma levels of PNU-96391A indicating that the effects observed are not related to pharmacokinetic interactions. These results suggest that PNU-96391A could be therapeutically useful to prevent the development of behavioral sensitization induced by DA agonists. 相似文献