全文获取类型
收费全文 | 1710篇 |
免费 | 60篇 |
国内免费 | 9篇 |
学科分类
医药卫生 | 1779篇 |
出版年
2024年 | 1篇 |
2023年 | 10篇 |
2022年 | 21篇 |
2021年 | 44篇 |
2020年 | 26篇 |
2019年 | 34篇 |
2018年 | 35篇 |
2017年 | 37篇 |
2016年 | 45篇 |
2015年 | 54篇 |
2014年 | 104篇 |
2013年 | 102篇 |
2012年 | 105篇 |
2011年 | 118篇 |
2010年 | 88篇 |
2009年 | 110篇 |
2008年 | 143篇 |
2007年 | 105篇 |
2006年 | 109篇 |
2005年 | 74篇 |
2004年 | 81篇 |
2003年 | 91篇 |
2002年 | 33篇 |
2001年 | 64篇 |
2000年 | 36篇 |
1999年 | 34篇 |
1998年 | 14篇 |
1997年 | 21篇 |
1996年 | 15篇 |
1995年 | 7篇 |
1994年 | 10篇 |
1993年 | 6篇 |
1990年 | 2篇 |
排序方式: 共有1779条查询结果,搜索用时 31 毫秒
81.
We compared the neuroprotective effects of the catecholestrogen 2-hydroxy-estradiol (2-OH-E2) to the actions of 17-β-estradiol (E2), since catecholestrogens have been clinically implicated in the pathophysiology of major depression and other psychiatric diseases. Using the hippocampal HT22 cell line as a well-established in vitro model system, we here show that the extent of the neuroprotective effects of 2-OH-E2 was significantly increased compared to the physiological estrogen E2 at equimolar concentrations after a toxic challenge with hydrogen peroxide. Statistically significant effects of neuroprotection as measured by survival of HT22 cells were detectable at concentrations of 1 and 10 μM of 2-OH-E2 or E2. Studies on the time-dependence of the evoked reactions showed that a pre-incubation and a post-incubation up to 30 min with a dose of 10 μM of 2-OH-E2 resulted in a significant decrease in cell death after incubation with hydrogen peroxide if compared to E2. Further characterization of the effects in rat brain homogenates with an assay for the induction of cellular lipid peroxidation (LPO) revealed, that 2-OH-E2 was more effective in the reduction of LPO than E2 in equimolar concentrations. This indicates a pharmacologically relevant effect of this hormone metabolite and a mechanism of action, which does not involve the classical estrogen receptor. In conclusion, the catecholestrogen 2-OH-E2 induces increased neuroprotective actions in comparison to the major physiological estrogen E2, suggesting a clinically relevant physiological function of catecholestrogens during health and disease. 相似文献
82.
83.
Barbara Wilhelm Holger Lüdtke Helmut Wilhelm 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2006,244(5):551-558
INTRODUCTION: Neuroprotection may be an option in ischemic optic nerve disease. There have been promising reports about the neuroprotective ability of topical brimonidine in animal studies. Therefore, we tested whether 0.2% brimonidine tartrate could improve the outcome of patients with non-arteritic anterior ischemic optic neuropathy (NAION). The study was stopped after an interim analysis, having not proven its feasibility within practicable time frame. METHODS: A 3-month, double-masked, placebo-controlled, randomised European multicenter trial conducted according to good clinical practice rules. Thirty-six patients (22 m, 14 f), older than 40 years with first eye involvement and typical signs of NAION were included in the study within the 1st week after visual loss (VA 0.05-1.0) and were randomized to treatment with either brimonidine 0.2% (Alphagan) or placebo. Visual acuity (VA, primary endpoint), visual field (VF, Humphrey 30-2 and Goldmann, quantified by a modified Esterman grid) and automated swinging flashlight test (SWIFT) were performed at baseline, 2 weeks, 4 weeks and 12 weeks after first visit. Primary analysis aimed at intention-to-treat group (ITT, n=29), secondary analysis to the per protocol population (PP, n=25). Tolerability and safety were tested in the safety group (n=36). A two-sample two-sided t-test was used for statistical analysis (alpha level at 0.05). RESULTS: VA did not show statistically significant difference by treatment. There were non-significant trends for better visual field results in the brimonidine group. Adverse events consisting of local irritation were observed six times in the verum and three times in the placebo group. No serious adverse events occurred. CONCLUSION: In contradiction to an open-labeled, retrospective study published by Fazzone et al., the results of this trial did not indicate any harmful effect of brimonidine in patients suffering from NAION. However, a statistically significant advantage for the patients receiving brimonidine tartrate could not be shown. 相似文献
84.
Dose-dependent protective effects of apomorphine against methamphetamine-induced nigrostriatal damage 总被引:6,自引:0,他引:6
(R)-apomorphine is a non-selective dopamine (DA) agonist which is used in the treatment of Parkinson's disease. In addition to symptomatic effects, apomorphine exerts a neuroprotective activity in specific experimental models. For instance, apomorphine prevents experimental parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroprotection obtained with apomorphine does not seem to be related to its dopamine (DA) agonist properties, instead it appears to be grounded on the antioxidant and the free radical scavenging effects of the compound. In this study, we sought to determine whether apomorphine protects against methamphetamine toxicity. We found that apomorphine (1; 5 and 10 mg/kg) dose-dependently protects against methamphetamine- (5 mg/kg X3, 2 h apart) induced striatal DA loss and reduction of tyrosine hydroxylase (TH) activity in the rat striatum. These protective effects are neither due to a decrease in the amount of striatal methamphetamine nor to hypothermia as indicated by measurement of striatal methamphetamine and body temperature at different time intervals after drug administration. The effects of apomorphine were neither opposite to, nor reversed by the DA antagonist haloperidol despite no decrease in body temperature was observed when apomorphine was given in combination with haloperidol. The present data are in line with recent studies suggesting a DA receptor-independent neuroprotective effect of apomorphine on DA neurons and call for further studies aimed at evaluating potential neuroprotective effects of apomorphine in Parkinson's disease. 相似文献
85.
Parkinson's disease (PD) is characterized by progressive degeneration of nigrostriatal dopaminergic neurons. Several factors such as inhibition of the mitochondrial respiration, generation of hydroxyl radicals and reduced free radical defense mechanisms causing oxidative stress, have been postulated to contribute to the degeneration of dopaminergic neurons. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated animals is a useful experimental model of PD, exhibiting most of the clinical features, as well as the main biochemical and pathologic symptoms of the disease. In the present study, we have examined a dopaminergic (D1) receptor agonist, SKF-38393 HCl (SKF) for its possible neuroprotective action against MPTP-induced insults on dopaminergic neurons. MPTP is converted by monoamine oxidase-B (MAO-B) to its neurotoxic metabolite 1-methyl-4-phenyl-pyridinium (MPP+), which is then taken up into the dopaminergic neurons. SKF-38393 had no effects either on total or monoamine oxidase B in the striatum. SKF-38393 blocked the MPTP-induced depletion of glutathione and attenuated MPTP-induced depletion of dopamine. Furthermore, it enhanced the activity of superoxide dismutase and hence mimicked the action of selegiline. The results of these studies are interpreted to suggest that SKF-38393 may prove a valuable drug in the treatment of Parkinson's disease. 相似文献
86.
Lipopolysaccharide-induced ischemic tolerance is associated with increased levels of ceramide in brain and in plasma 总被引:4,自引:0,他引:4
Zimmermann C Ginis I Furuya K Klimanis D Ruetzler C Spatz M Hallenbeck JM 《Brain research》2001,895(1-2):59-65
Intravenous administration of lipopolysaccharide (LPS) (0.9 mg/kg) has been shown to induce ischemic tolerance in spontaneously hypertensive rats (SHR). TNF-alpha is believed to play a crucial role in preconditioning as its inhibition with TNF-alpha-binding protein abolished tolerance. Our recent studies (Liu et al., Am. J. Physiol. 278 C144, 2000) have demonstrated that ceramide, a downstream messenger in TNF-alpha signaling, is a mediator of hypoxia-induced tolerance in neuronal cells. To test the hypothesis that ceramide contributes to LPS-induced tolerance in vivo, SHR were injected intravenously with either LPS or saline and the levels of ceramide in brain and in plasma were determined by reversed phase HPLC. LPS injection resulted in a significant increase of ceramide in plasma with a maximum at 24 h (8.32+/-1.14 pmol/microl (LPS) vs. 2.65+/-0.62 pmol/microl (saline)). LPS also induced ceramide upregulation in brain cortex, which started between 6 and 12 h and remained elevated up to 48 h after LPS injection. Fluorescent NBD-C6 ceramide was able to cross blood-brain barrier and was found in brain vessels, perivascular cells and in brain parenchyma 30 min after intravenous injection. These findings demonstrate that LPS preconditioning leads to elevation of ceramide in brain and plasma and, in conjunction with previous work, suggests that ceramide plays a role in LPS-induced protection against brain ischemic injury in vivo. 相似文献
87.
Gacyclidine, a channel blocker of N-methyl-D-aspartate receptors (NMDAR), exhibits potent neuroprotective properties and a low self-neurotoxicity. Preventing its interaction with NMDARs we demonstrate, through the use of its enantiomers, that gacyclidine also interacts with other ('non-NMDA') binding sites. The autoradiographic study showed that these sites displayed a uniform specific binding in the forebrain and a more discrete distribution in the molecular layer of the cerebellum. The 'non-NMDA' binding sites could exert a modulatory control on glutamatergic neurotransmission. 相似文献
88.
We used a 24 h perforant path stimulation model of status epilepticus to study the role of non-NMDA receptors in the loss of hilar interneurons and paired pulse inhibition associated with the model. In one experiment, NBQX administered i.v. at 1.0 mg/kg/h significantly reduced the loss of hematoxylin and eosin-stained hilar neurons from 360.2 to 125.3 but failed to protect against the loss of paired pulse inhibition. In a second experiment, i.v. NBQX at 1.5 mg/kg/h significantly protected against loss of SS- and NPY-positive hilar interneurons but also failed to protect against loss of paired pulse nhibition. These results demonstrate that the neuronal loss associated with sustained stimulation of this excitatory pathway is mediated in part through non-NMDA receptors. The lack of protection against loss of paired pulse inhibition suggests that SS- and NPY-immunoreactive interneurons may not be responsible for frequency-dependent paired-pulse inhibition of dentate granule cells. 相似文献
89.
结扎犬脑基底动脉后6h,发现脑干听觉诱发电位BAEP,各波的峰潜伏期(PL)及峰间期(IPL)明显延长(P<0.01);脑干神经元形态结构发生缺血性改变(光镜及电镜),脑干组织PLA2活性升高5.8倍(P<0.01),超氧化物歧化酶(SOD)活性降低58.8%(P<0.01)。海风藤300mg·kg-1、氟桂嗪1mp·kg-1、绞股蓝皂甙150mg·kg-1,分别于结扎脑基底动脉前3h经十二指肠造瘘管给药,皆能缩短PL及ⅠPL的延长(P<0.01),明显减轻神经元形态结构的缺血性改变,三者作用相当。与缺血组相比较,三药分别使PLA2活性降低80.2%。74.2%和72.4%(P<0.01),使SOD活性升高2.1、1.95和1.84倍(P<0.01)。上述结果提示三药抗脑缺血损伤的作用与其降低PLA2活性和增强SOD活性有关。 相似文献
90.
Melatonin plays a protective role in quinolinic acid-induced neurotoxicity in the rat hippocampus 总被引:2,自引:0,他引:2
The neuroprotective effect of melatonin against the quinolinic acid-induced degeneration of rat hippocampal neurons was investigated. Three groups of rats were given intrahippocampal injections of either; saline, quinolinic acid or i.p. injections of melatonin prior to and after being injected with quinolinic acid. On the fifth day after the intrahippocampal injections the brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor binding studies. The results show that melatonin protects hippocampal neurons from quinolinic acid-induced neurodegeneration and partially prevents the decrease in glutamate receptor numbers caused by quinolinic acid. Thus, melatonin has the potential to reduce hippocampal neuronal damage induced by neurotoxins such as quinolinic acid. 相似文献