全文获取类型
收费全文 | 1237篇 |
免费 | 124篇 |
国内免费 | 21篇 |
专业分类
儿科学 | 8篇 |
妇产科学 | 14篇 |
基础医学 | 180篇 |
口腔科学 | 3篇 |
临床医学 | 80篇 |
内科学 | 88篇 |
皮肤病学 | 6篇 |
神经病学 | 332篇 |
特种医学 | 12篇 |
外科学 | 46篇 |
综合类 | 103篇 |
预防医学 | 30篇 |
眼科学 | 3篇 |
药学 | 302篇 |
中国医学 | 112篇 |
肿瘤学 | 63篇 |
出版年
2024年 | 2篇 |
2023年 | 10篇 |
2022年 | 13篇 |
2021年 | 19篇 |
2020年 | 21篇 |
2019年 | 49篇 |
2018年 | 52篇 |
2017年 | 49篇 |
2016年 | 39篇 |
2015年 | 49篇 |
2014年 | 78篇 |
2013年 | 68篇 |
2012年 | 73篇 |
2011年 | 74篇 |
2010年 | 62篇 |
2009年 | 58篇 |
2008年 | 60篇 |
2007年 | 49篇 |
2006年 | 58篇 |
2005年 | 58篇 |
2004年 | 41篇 |
2003年 | 38篇 |
2002年 | 47篇 |
2001年 | 32篇 |
2000年 | 45篇 |
1999年 | 29篇 |
1998年 | 23篇 |
1997年 | 25篇 |
1996年 | 22篇 |
1995年 | 7篇 |
1994年 | 10篇 |
1993年 | 9篇 |
1992年 | 7篇 |
1991年 | 12篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1985年 | 15篇 |
1984年 | 14篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 8篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有1382条查询结果,搜索用时 62 毫秒
91.
Rumajogee P Vergé D Darmon M Brisorgueil MJ Hamon M Miquel MC 《Journal of neuroscience research》2005,81(4):481-487
Up-regulation of the neuronal serotoninergic phenotype in relation to astrocytic population was studied in primary cultures of rat embryonic rostral raphe. Short treatments (18 hr at day in vitro 4) with brain-derived neurotrophic factor (BDNF) or dibutyryl-cAMP (dBcAMP) increased the number of serotoninergic neurons by approximately 80% and approximately 40%, respectively, and markedly enhanced the branching (by 11-fold and 5-fold, respectively) and total length (by 4-fold and 2.5-fold, respectively) of their neurites. Concomitantly, under BDNF treatment, the astrocyte population was decreased by half and became mostly protoplasmic-like. In contrast, dBcAMP treatment also reduced the astrocytic cell density (by one-third) but induced a stellate morphology. Similar short treatment with the astrocyte-derived S100beta factor induced no modification of the serotonin (5-HT) neuronal phenotype nor of astrocytes morphology. Both BDNF- and cAMP-induced effects were abolished by simultaneous treatment with the specific tyrosine kinase inhibitor genistein, suggesting a role for the high-affinity BDNF receptor tyrosine kinase (TrkB). These data suggest that BDNF and cAMP, but not S100beta, rapidly induce both an up-regulation of the 5-HT neuronal phenotype and modifications of the neighboring astrocytes in a TrkB-dependent manner. 相似文献
92.
Antonelli T Fuxe K Tomasini MC Bartoszyk GD Seyfried CA Tanganelli S Ferraro L 《Synapse (New York, N.Y.)》2005,58(3):193-199
The effects of sarizotan, a 5-HT(1A) agonist with additional affinity for D(3) and D(4) receptors, have been studied on the corticostriatal glutamate pathways using dual-probe microdialysis in the awake rat. Sarizotan given systemically (0.1-10 mg/kg s.c.) or perfused into the motor cortex (10 microM) produced 20-30% reduction of cortical and striatal glutamate levels. The inhibitory effects of the systemic sarizotan on cortical and striatal glutamate levels were counteracted by intracortical perfusion with the 5-HT(1A) antagonist WAY100135 (10 microM). These findings suggest that the anti-dyskinetic properties of sarizotan could be mediated via its 5-HT(1A) agonist actions in the motor cortex, leading to reduced activity in the corticostriatal glutamate pathways with reduced activation of the striatopallidal GABA pathway mediating motor inhibition. 相似文献
93.
Serotonin is an important neurotransmitter that is involved in modulation of sensory, motor, and higher functions in many species. In the crayfish, which has been developed as a model for nervous system function for over a century, serotonin modulates several identified circuits. Although the cellular and circuit effects of serotonin have been extensively studied, little is known about the receptors that mediate these signals. Physiological data indicate that identified crustacean cells and circuits are modulated via several different serotonin receptors. We describe the detailed immunocytochemical localization of the crustacean type 1 serotonin receptor, 5-HT1crust, throughout the crayfish nerve cord and on abdominal superficial flexor muscles. 5-HT1crust is widely distributed in somata, including those of several identified neurons, and neuropil, suggesting both synaptic and neurohormonal roles. Individual animals show very different levels of 5-HT1crust immunoreactivity (5-HT(1crust)ir) ranging from preparations with hundreds of labeled cells per ganglion to some containing only a handful of 5-HT(1crust)ir cells in the entire nerve cord. The interanimal variability in 5-HT(1crust)ir is great, but individual nerve cords show a consistent level of labeling between ganglia. Quantitative RT-PCR shows that 5-HT1crust mRNA levels between animals are also variable but do not directly correlate with 5-HT(1crust)ir levels. Although there is no correlation of 5-HT1crust expression with gender, social status, molting or feeding, dominant animals show significantly greater variability than subordinates. Functional analysis of 5-HT1crust in combination with this immunocytochemical map will aid further understanding of this receptor's role in the actions of serotonin on identified circuits and cells. 相似文献
94.
Christodoulakos G Lambrinoudaki I Panoulis C Papadias C Economou E Creatsas G 《Fertility and sterility》2004,82(3):634-638
OBJECTIVE: To investigate the effect of continuous combined hormone therapy and raloxifene on serum VE-cadherin. DESIGN: The study was double blinded, with a placebo run-in period of 28-50 days. SETTING: University menopause clinic. PATIENT(S): Twenty-eight healthy postmenopausal women devoid of climacteric complaints. INTERVENTION(S): Subjects were randomized to 17beta-estradiol (2 mg) + norethisterone acetate (1 mg; E(2)-NETA) or raloxifene hCL (60 mg) for a period of 6 months. MAIN OUTCOME MEASURE(S): Serum VE-cadherin, which was estimated at baseline and at month 6. RESULT(S): Serum VE-cadherin decreased significantly in both E(2)-NETA and raloxifene groups (raloxifene baseline +/- SD: 1.17 +/- 0.44 ng/mL, 6 months: 0.82 +/- 0.29 ng/mL; E(2)-NETA baseline: 1.19 +/- 0.47 ng/mL, 6 months: 0.92 +/- 0.49 ng/mL). Percentage changes from baseline were -21.7 +/- 24.3 for E(2)-NETA and -26.0 +/- 20.6 for raloxifene. CONCLUSION(S): The effect of E(2)-NETA and raloxifene suggests that these drugs may preserve interendothelial junction integrity and control vascular permeability. Although this effect may influence the progress of the atheromatous lesion, its clinical impact on coronary artery disease (CAD) remains uncertain. 相似文献
95.
Effects of Cordyceps militaris extract on angiogenesis and tumor growth 总被引:21,自引:0,他引:21
INTRODUCTIONAngiogenesis is the process of new blood vesselformation from existing blood vessels and a natural re-sponse of tissues to ischemia[1]. The steps of angio-genesis involve proteolytic degradation of extracelluarmatrix, endothelial cell-matrix adhesion, migration,proliferation, and differentiation[2]. This biological re-action is often associated with some diseases, such assolid tumor[3], diabetic retinopathy[4], and rheumatoidarthritis[5].Tumor formation requires the developm… 相似文献
96.
Bartoszyk GD Van Amsterdam C Greiner HE Rautenberg W Russ H Seyfried CA 《Journal of neural transmission (Vienna, Austria : 1996)》2004,111(2):113-126
Summary. Sarizotan exhibited high affinities only to serotonin 5-HT1A receptors and dopamine DA D4>D3>D2 receptors with the profile of a 5-HT1A agonist and DA antagonist demonstrated by the inhibition of cAMP-stimulation and guinea pig ileum contraction, decreased accumulation of the 5-HT precursor 5-hydroxytryptophan and increased levels of 5-HT metabolites, increased accumulation of DA precursor dihydroxyphenylalanine (DOPA) and the reduced levels of DA metabolites in intact rats. However, sarizotan at higher doses decreased DA precursor accumulation in reserpinized rats and induced contralateral rotational behavior in unilaterally substantia nigra lesioned rats, indicating some intrinsic dopaminergic activity; at D2 receptors sarizotan may act as a partial agonist, depending on the dopaminergic impulse flow. Sarizotan represents a new approach for the treatment of extrapyramidal motor complications such as l-DOPA-induced dyskinesia in Parkinsons disease. 相似文献
97.
Paluchowska MH Bojarski AJ Bugno R Charakchieva-Minol S Wesołowska A 《Archiv der Pharmazie》2003,336(2):104-110
Structure-activity relationship studies of a series of novel 4, 6-disubstituted 2-(1-piperazinyl)pyridines were conducted to revise our model of serotonin 5-HT(2A) receptor antagonist. Target compounds were synthesized using the benzotriazole-assisted Katritzky method. The majority of those compounds were found to be selective 5-HT(2A)/5-HT(1A) receptor ligands, though less potent than their previously described pyrimidine counterparts. In particular, the three compounds 6-8 showed the highest 5-HT(2A) receptor affinity (K(i) = 34-78 nM) and were classified as 5-HT(2A) antagonists in in vivo experiments. The influence of the structural modifications on the in vitro results was discussed; however, the elucidation of the role of the central core system requires further studies. 相似文献
98.
A synthesis of two new active substances, DOMCl (1-(4-chloromethyl-2, 5-dimethoxyphenyl)-2-propanamine; 2) and DOMOM (1-(2, 5-dimethoxy-4-methoxymethylphenyl)-2-propanamine; 3), was developed. Unexpectedly, the Blanc reaction permitted successful synthesis of 2, 5-dimethoxyphenylpropylamine derivatives having a substituted methyl group in position 4 since solvation of the reactant occurs during the reaction. Afterwards, their affinities towards the 5-HT(2A) receptor were examined in 5-HT(2A) radioligand receptor binding assays. The study of these substances is of considerable interest because they were predicted, by preliminary molecular modeling studies based on mescalin units, to be potential new hallucinogens that should be added to the list of substances prohibited by law. It was assumed that DOMCl would be 82 times more potent as a hallucinogen than mescalin, and DOMOM would be 94 times more potent. The 5-HT(2A) radioligand receptor binding studies showed that the affinities of DOMCl and DOMOM for the 5-HT(2A) receptor are less than expected but are nevertheless 1.6 and 8.7 times higher, respectively, than that of mescalin. Therefore, scheduling these substances as potential drugs of abuse might be considered. 相似文献
99.
100.
Purpose. A new mucus-secreting in vitro drug absorption model based on monolayers of goblet-cell like sub-clones of the human colon carcinoma cell line HT29 obtained by methotrexate (MTX) treatment was investigated.
Methods. Twelve sub-clones were isolated and characterized by light microscopy (LM), transelectron microscopy (TEM), confocal laser scanning microscopy (CLSM), transepithelial electrical resistance (TEER) and the transport of a paracellular marker FITC-Dextran (Mw 4400) (FD-4).
Results. Significant differences of microscopical appearance, TEER-values and permeability of FD-4 between the sub-clones were evident. However, two of them, namely MTX-D1 and MTX-E12, formed tight confluent monolayers with a thick mucus-layer on the apical surface. They were used to compare the apparent permeability coefficient (Papp) of a series of lipophilic drugs, which should be affected by the mucus-layer, namely barbiturates (barbituric acid, barbital, phenobarbital, methylphenobarbital and heptabarbital) and testosterone, as a reference, to mucus-free Caco-2 cells. The permeability of drugs with a partition coefficient (log P) > 1 was decreased in the mucus-producing cell lines. Testosterone, the most lipophilic compound, showed a decrease of up to 43%.
Conclusions. We demonstrated that the mucus layer is a significant barrier to drug absorption for lipophilic drugs. In conclusion, our model may serve as a suitable in-vitro cell culture model to study the influence of the mucus layer on drug diffusion. 相似文献