全文获取类型
收费全文 | 393篇 |
免费 | 20篇 |
国内免费 | 1篇 |
专业分类
妇产科学 | 2篇 |
基础医学 | 25篇 |
口腔科学 | 1篇 |
临床医学 | 22篇 |
内科学 | 91篇 |
神经病学 | 8篇 |
特种医学 | 12篇 |
外科学 | 135篇 |
综合类 | 2篇 |
预防医学 | 10篇 |
眼科学 | 1篇 |
药学 | 89篇 |
中国医学 | 4篇 |
肿瘤学 | 12篇 |
出版年
2022年 | 1篇 |
2021年 | 5篇 |
2019年 | 5篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 4篇 |
2015年 | 6篇 |
2014年 | 17篇 |
2013年 | 18篇 |
2012年 | 24篇 |
2011年 | 25篇 |
2010年 | 16篇 |
2009年 | 12篇 |
2008年 | 38篇 |
2007年 | 37篇 |
2006年 | 33篇 |
2005年 | 24篇 |
2004年 | 22篇 |
2003年 | 19篇 |
2002年 | 28篇 |
2001年 | 8篇 |
2000年 | 6篇 |
1999年 | 8篇 |
1998年 | 10篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1981年 | 1篇 |
排序方式: 共有414条查询结果,搜索用时 0 毫秒
1.
Jean-yves Gillon Pierre-Alain Vitte Francoise Lemonnier Gabor Kato 《Drug development research》1994,32(1):42-49
Medifoxamine, an antidepressant agent which has an original chemical structure, has been shown through in vitro studies, utilising radioligand binding in tissue homogenates, to bind with moderately high affinity to 5-HT1c and 5-HT2 receptor subtypes and to 5-HT uptake sites (IC50 950, 980, and 1,500 nM, respectively). It has been shown to bind in vivo to rat brain 5-HT2 receptors after acute treatment with high dose (50 mg/kg, i.e., 133.9 μmol/kg). After 14 days continuous treatment with low dose (20 mg/kg, 53.6 μmol/kg), a decrease in the capacity of [3H]-5-HT uptake and a dose-dependent down-regulation of 5-HT2 receptors in rat cerebral cortex were observed. These results indicate that medifoxamine, which has been shown previously to act through dopaminergic systems, interacts also with central serotonergic neurotransmission and particularly with the 5-HT2 receptors, which could contribute to its antidepressant effect. 相似文献
2.
Evaluation and prediction of drug permeation 总被引:2,自引:0,他引:2
Pagliara A Reist M Geinoz S Carrupt PA Testa B 《The Journal of pharmacy and pharmacology》1999,51(12):1339-1357
A major challenge confronting the pharmaceutical scientist is to optimize the selective and efficient delivery of new active entities and drug candidates. Successful drug development requires not only optimization of specific and potent pharmacodynamic activity, but also efficient delivery to the target site. Following advances in rational drug design, combinatorial chemistry and high-throughput screening techniques, the number of newly discovered and promising active compounds has increased dramatically in recent years, often making delivery problems the rate-limiting step in drug research. To overcome these problems, a good knowledge of the pharmacokinetic barriers encountered by bioactive compounds is required. This review gives an overview of the properties of relevant physiological barriers and presents some important biological models for evaluation of drug permeation and transport. Physicochemical determinants in drug permeation and the relevance of quantitative and qualitative approaches to the prediction and evaluation of passive drug absorption are also discussed. 相似文献
3.
Mariusz Papp Piotr Gruca Pierre-Alain Boyer Elisabeth Moca?r 《Neuropsychopharmacology》2003,28(4):694-703
Chronic mild stress (CMS), a well-validated model of depression, was used to study the effects of the melatonin agonist and selective 5-HT(2C) antagonist agomelatine (S 20098) in comparison with melatonin, imipramine, and fluoxetine. All drugs were administered either 2 h before (evening treatment) or 2 h after (morning treatment) the dark phase of the 12-h light/dark cycle. Chronic (5 weeks) evening treatment with agomelatine or melatonin (both at 10 and 50 mg/kg i.p.) dose-dependently reversed the CMS-induced reduction in sucrose consumption. The magnitude and time course of the action of both drugs was comparable to that of imipramine and fluoxetine (both at 10 mg/kg i.p.); however, melatonin was less active than agomelatine at this dose. The effect of evening administration of agomelatine and melatonin was completely inhibited by an acute injection of the MT(1)/MT(2) antagonist, S 22153 (20 mg/kg i.p.), while the antagonist had no effect in animals receiving fluoxetine or imipramine. When the drugs were administered in the morning, agomelatine caused effects similar to those observed after evening treatment (with onset of action faster than imipramine) but melatonin was ineffective. Moreover, melatonin antagonist, S 22153, did not modify the intakes in stressed animals receiving morning administration of agomelatine and in any other control and stressed groups tested in this study. These data demonstrate antidepressant-like activity of agomelatine in the rat CMS model of depression, which was independent of the time of drug administration. The efficacy of agomelatine is comparable to that of imipramine and fluoxetine, but greater than that of melatonin, which had no antidepressant-like activity after morning administration. While the evening efficacy of agomelatine can be related to its melatonin receptors agonistic properties, its morning activity, which was not inhibited by a melatonin antagonist, indicates that these receptors are certainly required, but not sufficient to sustain the agomelatine efficacy. It is therefore suggested that the antidepressant-like activity of agomelatine depends on some combination of its melatonin agonist and 5-HT(2C) antagonist properties. 相似文献
4.
5.
David Eric Ouedraogo Alain Makinson Nils Kuster Nicolas Nagot Pierre-Alain Rubbo Karine Bollore Vincent Foulongne Guillaume Cartron Daniel Olive Jacques Reynes Jean-Pierre Vendrell Edouard Tuaillon 《Journal of clinical immunology》2013,33(1):22-29
Background
Despite the use of combined antiretroviral therapy, HIV-infected individuals have a higher risk of developing B-cell lymphoma compared to the general population. We aim to explore whether lymphocyte activation, increase in Th1 response as well as markers of EBV reactivation, may precede lymphoma diagnosis.Methods
Thirteen cases and 26 controls matched on CD4+ T-cell count and HIV plasma viral load were identified. Samples were collected 0 to 5 years prior to B-cell lymphoma diagnosis. Seven out of 13 (54 %) and 16/26 (61.5 %) of cases and controls were receiving antiretroviral therapy at the time of sampling, respectively. CD8+ T-cell activation and Th1 cytokine concentrations were measured before lymphoma onset, together with IgG antibodies directed against viral capsid antigen (VCA) and serum levels of EBV DNA.Results
A higher level of CD8+ T-cell activation was observed in patients developing lymphoma. Four out of seven Th1 cytokine serum concentrations were significantly higher in patients with lymphoma than in the control group: IL-2R, IL-12p40/70, IFN-γ-inducible protein 10 (IP-10) and monokine induced by IFN-γ (MIG). Anti-VCA IgG level were significantly higher in cases than in controls. Four cases (30 %) but no controls had detectable EBV DNA in serum.Conclusion
A higher level of T-cell activation, Th1 cytokine serum concentration and markers of EBV replication, preceded B-cell lymphoma diagnosis. This may suggest that viral antigen stimulation is associated with the genesis of lymphoma in HIV-infected patients. 相似文献6.
7.
8.
9.
10.
Vibration applied to the Achilles tendon is well known to induce in freely standing subjects a backward body displacement and in restrained subjects an illusory forward body tilt. The purpose of the present experiment was to evaluate the effect of Achilles tendon vibration (90Hz) on postural orientation in subjects free of equilibrium constraints. Subjects (n=12) were strapped on a backboard that could be rotated in the antero-posterior direction with the axis of rotation at the level of the ankles. They stood on a rigid horizontal floor with the soles of their feet parallel to the ground. They were initially positioned 7 degrees backward or forward or vertical and were required to adjust their body (the backboard) to the vertical orientation via a joystick. Firstly, results showed that in response to Achilles tendon vibration, subjects adjusted their body backward compared to the condition without vibration. This backward body adjustment likely cancel the appearance of an illusory forward body tilt. It was also observed that the vibratory stimulus applied to the Achilles tendon elicited in restrained standing subjects an increased EMG activity in both the gastrocnemius lateralis and the soleus muscles. Secondly, this vibration effect was more pronounced when passive displacement during the adjustment phase was congruent with the simulated elongation of calf muscles. These results indicated that the perception of body orientation is coherent with the postural response classically observed in freely standing subjects although the relationship between these two responses remains to be elucidated. 相似文献