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91.
92.
Sapozhnikova TA Zarudiĭ FS Baschenko NZh Makara NS Khisamutdinova RIu Gabdrakhmanova SF Ivanova NA Nazarov VS 《Eksperimental'naia i klinicheskaia farmakologiia》2007,70(4):30-31
2-Demethoxycarbonyl-2-ethoxycarbonyl-11-deoxymisoprostol (11-DMP) produces antioxidant effect on the models of toxic hepatitis induced by paracetamol and carbon tetrachloride. The drug normalizes the lipid peroxidation (LPO) prosess in rat liver of the rat and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the rat blood, thus demonstrating hepatoprotective action. 相似文献
93.
RJ Mann NE Nasr JK Sinfield E Paci D Donnelly 《British journal of pharmacology》2010,160(8):1973-1984
BACKGROUND AND PURPOSE
Exendin-4 (exenatide, Ex4) is a high-affinity peptide agonist at the glucagon-like peptide-1 receptor (GLP-1R), which has been approved as a treatment for type 2 diabetes. Part of the drug/hormone binding site was described in the crystal structures of both GLP-1 and Ex4 bound to the isolated N-terminal domain (NTD) of GLP-1R. However, these structures do not account for the large difference in affinity between GLP-1 and Ex4 at this isolated domain, or for the published role of the C-terminal extension of Ex4. Our aim was to clarify the pharmacology of GLP-1R in the context of these new structural data.EXPERIMENTAL APPROACH
The affinities of GLP-1, Ex4 and various analogues were measured at human and rat GLP-1R (hGLP-1R and rGLP-1R, respectively) and various receptor variants. Molecular dynamics coupled with in silico mutagenesis were used to model and interpret the data.KEY RESULTS
The membrane-tethered NTD of hGLP-1R displayed similar affinity for GLP-1 and Ex4 in sharp contrast to previous studies using the soluble isolated domain. The selectivity at rGLP-1R for Ex4(9–39) over Ex4(9–30) was due to Ser-32 in the ligand. While this selectivity was not observed at hGLP-1R, it was regained when Glu-68 of hGLP-1R was mutated to Asp.CONCLUSIONS AND IMPLICATIONS
GLP-1 and Ex4 bind to the NTD of hGLP-1R with similar affinity. A hydrogen bond between Ser32 of Ex4 and Asp-68 of rGLP-1R, which is not formed with Glu-68 of hGLP-1R, is responsible for the improved affinity of Ex4 at the rat receptor. 相似文献94.
Background
Malaria is a leading cause of mortality in Uganda accounting for 25% of deaths among children. Hitherto no adjunct therapy has been identified to improve outcome of cerebral malaria. Retinol suppresses growth of P.falciparum, scavenges free radicals, and exhibits synergistic action with quinine in parasite clearance.Objective
To determine the effect of vitamin A supplementation on treatment outcome of cerebral malariaMethods
In this randomised double-blind placebo controlled clinical trial we studied 142 children aged 6–59 months admitted with cerebral malaria in Mulago Hospital, Kampala. Children were randomised to either vitamin A or placebo and followed for 7 days. The main outcome measures were coma recovery time, time for convulsions to stop, and parasite and fever clearance. Secondary outcomes were overall mortality and time taken to start oral feeds.Results
There was no difference in the coma recovery time (p=0.44), resolution of convulsions (p=0.37), fever clearance (p=0.92), parasite clearance (p=0.12), and starting oral feeds between the two treatment groups. Mortality was higher (16.2%) in the placebo than in the vitamin A group (8.1%): RR 1.4; 95% CI 1.0–2.1.Conclusions
Vitamin A as adjunct therapy did not significantly reduce coma duration but there were fewer deaths in the vitamin A arm. 相似文献95.
96.
Rats were injected intraperitoneally with corticosterone (1 mg/kg). Ten min later they were submitted to dyadic encounters for 15 min. Rats naive to aggressive encounters responded to the corticosterone treatment by a reduction in resting times and an increase in exploration directed towards the novel environment. Resident rats acquainted with aggressive encounters responded to the treatment by a reduction of resting and an increase in threat behaviours. In resident rats acquainted with aggressive encounters and reared previously with a female an increase in attack frequency was noticed. It is concluded that an acute increase in blood corticosterone results in a stimulation of behaviour during social challenge, however, the specific effect is highly context dependent. These data confirm sporadic reports that noticed a behavioural stimulatory effect of acute corticosterone treatments. However, as far as a social challenge situation is concerned, the effect of corticosterone seems to be rather context then behaviour specific. Since corticosterone is known rather to change neuronal excitability than to activate neurons by itself, one can hypothesize that the context dependency of the effect is determined by the different configuration of activated centres in different situations. Attack may be stimulated by corticosterone only when centres involved in attack are already activated, that is, when a high frequency of attack is already present. 相似文献
97.
Many neurons express simultaneously two or more isotypes of glutamate receptors, so that pharmacological modulation of more than one receptor may be necessary to reveal the role of glutamate in mediating physiological processes. The present studies were aimed at evaluating involvement of endogenous glutamate in triggering plasma prolactin (PRL) and adrenocorticotropic hormone (ACTH) levels in response to three different stress stimuli (footshock, immobilization and ether stress). Blockade of glutamate receptor subtypes was achieved by the administration of the NMDA antagonist dizocilpine (MK-801, 0.2 mg/kg) and the selective AMPA antagonist GYKI 52466 (10 mg/kg). Rats were pretreated for 4-5 days and then exposed to stressful stimulation. Basal hormone levels were not affected by the antagonists. In male rats, combined, but not separate blockade of NMDA and AMPA/kainate subtypes of glutamate receptors prevented the rise in plasma PRL in response to footshock stress. In female rats, footshock-induced PRL release was inhibited even by separate blockade of NMDA receptors by dizocilpine, suggesting that the PRL system of females is more sensitive to the effect of NMDA antagonists than that of males. None of the treatments affected PRL release during immobilization or ether stress. Simultaneous blockade of NMDA and AMPA receptor subtypes resulted in a mild inhibition of immobilization-induced ACTH release without any effect on ACTH response to footshock or ether stress. The data suggest that involvement of glutamatergic pathways in neuroendocrine response during stress is selective for discrete stress stimuli and stress hormones. In addition a concerted action of glutamate on both NMDA and non-NMDA receptor subtypes is involved in the control of PRL release during footshock stress. 相似文献
98.
99.
We tested the effect of cholinergic drugs on the concentration of intracellular free calcium in rat melanotropes. Acetylcholine, muscarine, carbachol, and nicotine resulted in a significant rise in this parameter. Effect of acetylcholine was reduced by atropine (non-selective muscarinic antagonist), pirenzepine (M1 muscarinic antagonist), and 4-DAMP (M3 > M1 muscarinic antagonist), but exposure to the M1 muscarinic agonist McN-A 343 resulted in a significantly smaller calcium-response than that seen in response to acetylcholine or to muscarine. This suggests the involvement of both M1 and M3 muscarinic receptors in the acetylcholine-induced calcium-rise. On the other hand, in the presence of atropine the acetylcholine-induced calcium-rise was not eliminated: this fact indicates that nicotinic receptors are also involved in the acetylcholine-induced intracellular calcium-rise. The acetylcholine-, and nicotine-induced calcium-rise was significantly reduced in presence of the neuronal-type nicotinic antagonist, mecamylamine. This suggests the involvement of a neuronal-type nicotinic receptor in the acetylcholine-induced intracellular calcium-response. Moreover, because in a further experiment almost 80% of the cells investigated responded to muscarine as well as nicotine, we conclude that both functionally active muscarinic and nicotinic receptors are present on the same cell. 相似文献
100.
Baschenko NZh Sapozhnikova TA Gabdrakhmanova SF Makara NS Khisamutdinova RY Zarudii FS Ivanova NA Nazarov VS 《Bulletin of experimental biology and medicine》2006,142(4):467-469
11-Deoxymisoprostol (prostaglandin E1 analog) exhibited a pronounced gastroprotective effect on various models of experimental
ulcers induced by nonsteroid antiinflammatory drugs. A relationship between high resistance of the gastroduodenal mucosa under
the effect of 11-deoxymisoprostol and changes in the level of sialic acid was detected.
__________
Translated From Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 10, pp. 451–453, October, 2006 相似文献