全文获取类型
收费全文 | 481篇 |
免费 | 32篇 |
国内免费 | 27篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 24篇 |
妇产科学 | 2篇 |
基础医学 | 49篇 |
口腔科学 | 15篇 |
临床医学 | 49篇 |
内科学 | 87篇 |
皮肤病学 | 5篇 |
神经病学 | 44篇 |
特种医学 | 36篇 |
外科学 | 41篇 |
综合类 | 8篇 |
预防医学 | 37篇 |
眼科学 | 32篇 |
药学 | 89篇 |
肿瘤学 | 20篇 |
出版年
2024年 | 1篇 |
2023年 | 2篇 |
2022年 | 9篇 |
2021年 | 19篇 |
2020年 | 15篇 |
2019年 | 11篇 |
2018年 | 15篇 |
2017年 | 9篇 |
2016年 | 10篇 |
2015年 | 18篇 |
2014年 | 15篇 |
2013年 | 14篇 |
2012年 | 29篇 |
2011年 | 27篇 |
2010年 | 25篇 |
2009年 | 23篇 |
2008年 | 22篇 |
2007年 | 38篇 |
2006年 | 22篇 |
2005年 | 22篇 |
2004年 | 11篇 |
2003年 | 11篇 |
2002年 | 9篇 |
2001年 | 17篇 |
2000年 | 14篇 |
1999年 | 7篇 |
1998年 | 10篇 |
1997年 | 12篇 |
1996年 | 8篇 |
1995年 | 4篇 |
1994年 | 8篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 7篇 |
1988年 | 11篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有540条查询结果,搜索用时 0 毫秒
1.
2.
3.
4.
R A Adan A W Szklarczyk J Oosterom J H Brakkee W A Nijenhuis W M Schaaper R H Meloen W H Gispen 《European journal of pharmacology》1999,378(3):249-258
Since the melanocortin MC3 and melanocortin MC4 receptors are the main melanocortin receptor subtypes expressed in rat brain, we characterized the activity and affinity of nine melanocortin receptor ligands using these receptors in vitro, as well as their activity in a well-defined melanocortin-induced behavior in the rat: grooming behavior. We report here that [D-Tyr4]melanotan-II and RMI-2001 (Ac-cyclo-[Cys4, Gly5, D-Phe7, Cys10]alpha-MSH-NH2) have significantly higher affinity and potency on the rat melanocortin MC4 receptor as compared to the rat melanocortin MC3 receptor. Nle-gamma-MSH (melanocyte-stimulating hormone) was the only ligand with higher affinity and potency on the rat melanocortin MC3 receptor. The potency order of melanocortin MC4 receptor agonists, but not that of melanocortin MC3 receptor agonists, fitted with the potency of these ligands to stimulate grooming behavior, when administered intracerebroventricularly. SHU9119 (Ac-cyclo-[Nle4, Asp5, D-Nal(2)7, Lys10]alpha-MSH-(4-10)-NH2) and RMI-2005 (Ac-cyclo-[Cys4, Gly5, D-Na](2)7, Nal(2)9, Cys10]alpha-MSH-(4-10)-NH2) were able to inhibit alpha-MSH-induced melanocortin receptor activity in vitro, as well as alpha-MSH-induced grooming behavior. Melanotan-II, [Nle4-D-Phe7]alpha-MSH and RMI-2001 were also effective in inducing grooming behavior when administered intravenously. In the absence of purely selective melanocortin MC(3/4) receptor ligands, we demonstrated that careful comparison of ligand potencies in vitro with ligand potencies in vivo, could identify which melanocortin receptor subtype mediated alpha-MSH-induced grooming behavior. Furthermore, blockade of novelty-induced grooming behavior by SHU9119 demonstrated that this physiological stress response is mediated via activation of the melanocortin system. 相似文献
5.
Puig N Dávalos A Adan J Piulats J Martínez JM Castillo J 《Cerebrovascular diseases (Basel, Switzerland)》2000,10(6):449-454
BACKGROUND AND PURPOSE: High levels of glutamate in plasma and cerebrospinal fluid (CSF) have been demonstrated in patients with acute ischemic stroke. Whereas this glutamate increase in CSF is only evidenced during the first 6 h in stable ischemic stroke, it is sustained for 24 h in progressing stroke. The aim of this investigation was to study the evolution of serum glutamate levels after stroke in a rat model of permanent cerebral artery occlusion. METHODS: Glutamate, glycine, aspartate, taurine and tryptophan were measured by high-performance liquid chromatography from serum samples taken before and at different times after permanent middle cerebral artery occlusion (MCAO) and from sham-operated rats. RESULTS: After MCAO, a 3-fold increase in glutamate and a 2-fold increase in glycine and aspartate were observed in rat serum. The onset of this amino acid increase began 4-6 h after ischemic induction, reached peak values at 8-24 h and returned to preischemic values by 48-72 h. Serum concentrations of taurine and tryptophan were not modified after MCAO. Sham-operated rats did not exhibit changes of basal amino acid concentrations in serum. CONCLUSIONS: The serum excitatory amino acid profile in this experimental model confirms that the early detection of increased concentrations of glutamate and glycine at systemic circulation observed in patients with acute stroke is a consequence of the cerebral ischemic process. 相似文献
6.
Murray JF Mercer JG Adan RA Datta JJ Aldairy C Moar KM Baker BI Stock MJ Wilson CA 《Journal of neuroendocrinology》2000,12(11):1133-1139
The adipose hormone, leptin, not only restrains appetite, but also influences energy expenditure. One such influence is to promote sexual maturation and fertility. The neuromodulatory circuits that mediate this effect are not well known but the present study suggests that one mediator could be melanin-concentrating hormone (MCH). We show that the long-form receptor (Ob-Rb) is expressed in the zona incerta of the rat and that administration of leptin (both 0.5 microg and 1.0 microg/side) into this area of ovariectomized, oestrogen-primed rats stimulated the release of luteinizing hormone (LH) within 1 h, the effect enduring for a further 1 h. Injections of leptin into the arcuate nucleus induced a smaller, transient rise in LH while injections into the paraventricular and ventromedial nuclei were without effect. MCH neurones are present in the zona incerta and administration of this hormone into the medial preoptic area (mPOA) stimulates LH release, therefore we investigated the possibility that MCH might mediate this effect of leptin. An injection of MCH antiserum into mPOA prevented the rise in LH normally induced by leptin injected into the zona incerta. In addition, melanocortin receptor antagonists ([D-Arg8]ACTH(4-10) and [Ala6]ACTH(4-10)), previously shown to inhibit the stimulatory effect of MCH on LH release, also inhibited the effect of leptin. We propose that one route by which leptin may promote reproductive activity is by enhancing MCH release from fibres within the mPOA. Speculative mechanisms for the action of MCH include the following possibilities: MCH may be acting on the specific MCH receptor which in turn interacts with a melanocortin or melanocortin-like receptor; MCH may bind directly to one of the melanocortin receptors; or melanocortin antagonists may interact with the MCH receptor. 相似文献
7.
8.
9.
Expression of fibrinogen receptors during activation and subsequent desensitization of human platelets by epinephrine 总被引:2,自引:0,他引:2
Epinephrine causes platelet aggregation and secretion by interacting with alpha 2-adrenergic receptors on the platelet surface. Platelet aggregation requires the binding of fibrinogen to a specific receptor on the membrane glycoprotein IIb-IIIa complex. Although the IIb-IIIa complex is identifiable on the surface of resting platelets, the fibrinogen receptor is expressed only after platelet activation. The current studies were designed to examine the effect of occupancy of platelet alpha 2-adrenergic receptors by epinephrine on the expression of fibrinogen receptors and on the aggregation of platelets. The ability of epinephrine to induce the expression of fibrinogen receptors was studied under two different conditions: acute stimulation (less than 1 min) and prolonged stimulation (50 to 90 min), the latter of which is associated with a reduction or "desensitization" of the platelet aggregation response. Expression of the fibrinogen receptor was monitored with 125I-fibrinogen as well as with 125I-PAC-1 (PAC-1), a monoclonal antibody that binds to the glycoprotein IIb-IIIa complex only after platelets are activated. Epinephrine caused an immediate increase in PAC-1 and fibrinogen binding that was dependent on occupancy of the alpha 2-receptor by epinephrine and on the presence of extracellular free Ca (KCa = 30 mumol/L). By itself, 1 mmol/L Mg was unable to support induction of the fibrinogen receptor by epinephrine. However, it did decrease the Ca requirement by about two orders of magnitude. Prolonged stimulation of unstirred platelets by epinephrine led to a 70% decrease in the aggregation response when the platelets were subsequently stirred. Despite their decreased aggregation response, desensitized platelets bound PAC-1 and fibrinogen normally, indicating that the loss of aggregation was not due simply to a decrease in fibrinogen receptor expression. Although desensitization was not affected by pretreatment of the platelets with aspirin, it was partially prevented when extracellular Ca was chelated by EDTA during the long incubation with epinephrine. These studies demonstrate that once platelet alpha 2-adrenergic receptors are occupied by epinephrine, extracellular Ca is involved in initiating the aggregation response by supporting the induction of the fibrinogen receptor and the binding of fibrinogen. Furthermore. Ca-dependent reactions subsequent to fibrinogen binding may be necessary for maximal platelet aggregation and are impaired when platelets become desensitized to epinephrine. 相似文献
10.
Two patients with progressive hairy cell leukemia following splenectomy were treated with low-dose daily chlorambucil. Both had an objective hematologic response as determined by a return to normal hematocrit and platelet count. This was also reflected in the mononuclear cell fraction by the normalization of cholesterol content, cholesterol/phospholipid ratio, and the lymphocyte subpopulations. This article confirms previous reports on the efficacy of chlorambucil in this setting and describes some morphological, and biochemical concomitant events. 相似文献