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排序方式: 共有227条查询结果,搜索用时 31 毫秒
61.
Volbracht C van Beek J Zhu C Blomgren K Leist M 《The European journal of neuroscience》2006,23(10):2611-2622
The pathogenesis of stroke, trauma and chronic degenerative diseases, such as Alzheimer's disease (AD), has been linked to excitotoxic processes due to inappropriate stimulation of the N-methyl-D-aspartate receptor (NMDA-R). Attempts to use potent competitive NMDA-R antagonists as neuroprotectants have shown serious side-effects in patients. As an alternative approach, we were interested in the anti-excitotoxic properties of memantine, a well-tolerated low affinity uncompetitive NMDA-R antagonist presently used as an anti-dementia agent. We explored in a series of models of increasing complexity, whether this voltage-dependent channel blocker had neuroprotective properties at clinically relevant concentrations. As expected, memantine protected neurons in organotypic hippocampal slices or dissociated cultures from direct NMDA-induced excitotoxicity. However, low concentrations of memantine were also effective in neuronal (cortical neurons and cerebellar granule cells) stress models dependent on endogenous glutamate stimulation and mitochondrial stress, i.e. exposure to hypoxia, the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+) or a nitric oxide (NO) donor. Furthermore, memantine reduced lethality and brain damage in vivo in a model of neonatal hypoxia-ischemia (HI). Finally, we investigated functional rescue (neuronal capacity to migrate along radial glia) by memantine in cerebellar microexplant cultures exposed to the indirect excitotoxin 3-nitropropionic acid (3-NP). Potent NMDA-R antagonists, such as (+)MK-801, are known to block neuronal migration in microexplant cultures. Interestingly, memantine significantly restored the number of neurons able to migrate out of the stressed microexplants. These findings suggest that inhibition of the NMDA-R by memantine is sufficient to block excitotoxicity, while still allowing some degree of signalling. 相似文献
62.
目的从病理学角度探讨1-氨基-3,5-二甲基金刚烷(美金胺)对新生大鼠各主要脏器可能造成的毒性影响。方法新生大鼠68只随机分为7组,分别腹腔注射不同剂量的美金胺和注射用水,对所有死亡新生大鼠及时尸解,存活新生大鼠在给药7 d后断头处死,取肝、肾、脑、心、肺、脾进行病理检查,评估不同剂量的美金胺对重要脏器的可能毒性改变。结果1.用药组死亡新生大鼠脑、肝的脏体较正常7日龄新生大鼠相应脏器的脏体比显著增高,脾脏较正常7日龄新生大鼠相应脏器的脏体比显著减低。2.镜下病理检查结果显示,脑组织有神经元变性,肝组织有淤血和细胞变性,余脏器病变不明显。3.新生大鼠的病理变化程度及死亡率与美金胺的剂量呈正相关。结论美金胺对新生大鼠的脑和肝脏影响较大。 相似文献
63.
W. Danysz M. Gossel W. Zajaczkowski D. Dill G. Quack 《Journal of neural transmission (Vienna, Austria : 1996)》1994,7(3):155-166
Summary Amantadine (25, 50, 100 mg/kg), memantine (5, 10, 20 mg/kg) and MK-801 (0.05, 0.1, 0.2 mg/kg), all having NMDA channel blocking properties, were compared in three tests used for screening of antiparkinsonian agents in rats, namely: haloperidol-induced catalepsy, locomotor activity in monoamine depleted rats and rotation in rats with a unilateral substantia nigra lesion. Additionally, plasma levels of amantadine and memantine were assessed to gain an insight into the concentration ranges achieved at behaviorally active doses. Amantadine and (+)-MK-801 produced dosedependent inhibition of haloperidol-induced catalepsy while memantine was less efficacious producing clear-cut anticataleptic action at a dose of 10 mg/kg only but failing at 20 mg/kg due to myorelaxant activity. All agents attenuated sedation in monoamine depleted rats with amantadine being the least and MK-801 being the most effective. The same rank order of efficacy was seen in inducing ipsilateral rotations in rats after a substantia nigra lesion. On the basis of the present study and published data, it can be assumed that the doses of amantadine, memantine and MK-801 showing antiparkinsonian-like activity in animals result in plasma levels leading to NMDA antagonism. However, in the haloperidol-induced catalepsy test the efficacy of amantadine was higher than memantine, while the opposite was true for rotation and reserpine-induced sedation indicating pharmacodynamic differences between both agents. 相似文献
64.
高效液相色谱法测定盐酸美金刚烷胺片的含量 总被引:3,自引:0,他引:3
目的建立HPLC测定盐酸美金刚烷胺片含量的方法.方法采用 Hypersil ODS柱(250 mm×4.6 mm,5 μm)为固定相,流动相为0.33%磷酸氢二钾溶液-乙腈(40∶60,v/v);检测波长为197 nm;流速为1.5 mL·min-1;柱温30 ℃.结果本方法在0.5~2.0 mg·mL-1呈良好线性关系(r=0.999 9),进样重现性RSD为1.08%(n=5),平均回收率为98.50%,日内RSD为1.68%(n=5),日间RSD为1.82%(n=5).结论本方法简便、快速,结果准确可靠,可用于盐酸美金刚烷胺片的含量测定. 相似文献
65.
Lermontova NN Mukhina TV Van'kin GI Serkova TP Bachurin SO 《Bulletin of experimental biology and medicine》2003,135(1):48-51
Systemic oral administration of NT-0409, a new synthetic agonist of AMPA subtype glutamate receptor, to rats with chronic partial AF64A-induced deprivation of cholinergic functions improved their learning in a Morris water maze. NT-0409 is close to memantine by the effect on learning and, in contrast to cholinomimetic arisept, ensures longer retention of the developed habit. 相似文献
66.
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68.
A disturbed cellular calcium homeostasis is suggested to play a pivotal role in neuronal damage. Energy deficiency causes depolarization of the neuronal membrane and Ca2+ enters the cells through different ion channels, the voltage-sensitive L-type Ca2+ channels and the NMDA-operated channels being the main gates. In the present study we used primary cultures of rat hippocampal neurons to demonstrate that the dihydropyridine calcium antagonist nimodipine, the non-competitive NMDA antagonists dizocilpine and memantine, as well as the AMPA antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline), attenuate the glutamate-induced neuronal damage dose-dependently. Nimodipine applied simultaneously with NMDA-antagonists and NBQX, respectively, resulted in somewhat greater neuroprotection of glutamate-treated neurons compared with the effects of these agents applied singly. The type of interaction is best described by an independent action in combination, which means that the relative effects of nimodipine were not enhanced. Therefore, it can be considered as a lack of potentiation. © 1997 Elsevier Science Ltd. All rights reserved. 相似文献
69.
Casson RJ 《Clinical & experimental ophthalmology》2006,34(1):54-63
Excitotoxicity describes the process of neuronal injury by excess stimulation of amino acid receptors. This form of insult was first described in the retina, and subsequently has been shown to be an important component of the pathogenesis of ischaemic and traumatic injury in the central nervous system. Furthermore, there is increasing evidence that excitotoxicity is involved in several chronic neurological conditions, and anti-excitotoxic treatment has already been approved for some of these conditions. A large-scale trial is currently underway that will determine the efficacy of an anti-excitotoxic drug (memantine) in the management of glaucoma. This review provides an overview of neurotransmission and the mechanisms of excitotoxicity. The evidence for excitotoxicity as a component of certain neurological diseases, including glaucoma, is discussed. 相似文献
70.
目的评价美金刚胶囊剂与片剂的人体生物等效性。方法20名健康男性受试者采用随机交叉实验设计,用高效液相色谱-质谱联用法,测定单剂量口服美金刚胶囊剂与片剂各10 mg后美金刚的血浆浓度,所得数据经DAS 2.0软件处理获得各自的药动学参数。结果美金刚胶囊和片剂的主要药动学参数:t_(max)分别为(6.1±s 2.4)和(6.6±2.6)h,c_(max)分别为(13±3)和(12±4)μg·L~(-1),t_(1/2)分别为(63±14)和(64±12)h;用梯形法计算,AUC_(0~1)分别为(902±292)和(845±256)μg·h·L~(-1);以AUC_(0~1)计算,美金刚胶囊剂的平均相对生物利用度为(110±28)%。统计学分析结果表明胶囊剂与片剂的主要药动学参数c_(max)、AUC_(0~1)和t_(max)均无显著差异。结论2种制剂在人体内具有生物等效性。 相似文献