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排序方式: 共有224条查询结果,搜索用时 15 毫秒
31.
Tomas Pavlik Eva Janousova Jiri Mayer Karel Indrak Marie Jarosova Hana Klamova Daniela Zackova Jaroslava Voglova Edgar Faber Michal Karas Katerina Machova Polakova Zdenek Racil Eva Demeckova Ludmila Demitrovicova Elena Tothova Juraj Chudej Imrich Markuljak Eduard Cmunt Tomas Kozak Jan Muzik Ladislav Dusek 《American journal of hematology》2013,88(9):790-797
32.
The objective of the present study was to explore if lesions of the ascending noradrenergic pathways, originating in the locus coeruleus, modulate the cerebral metabolic response to bicuculline-induced seizures in rats. Bilateral noradrenergic lesions were performed by 6-hydroxydopamine injections in the caudal mesencephalon, 12–22 days before seizures were induced in animals ventilated on N2O:O2 (75:25). After 5 min of seizures the brain was frozen in situ and cerebral cortex and hippocampus were sampled for analysis. Labile phosphates, glycolytic metabolites, cyclic nucleotides, and free fatty acids were measured. In another series, lesioned animals were used for measurements of cerebral oxygen consumption.The noradrenergic lesions neither modified the electroencephalographically recorded seizure discharge, nor did they alter cerebral oxygen consumption or cerebral energy state. However, when compared to sham-operated animals, those with noradrenergic lesions had significantly higher (115% and 68%) glycogen concentrations and lower (50% and 52%) cyclic AMP concentrations in cerebral cortex and hippocampus, respectively, demonstrating the marked influence of noradrenergic activity on adenylate cyclase activity and glycogenolysis. The lesions failed to modulate the rise in free fatty acids in the cerebral cortex, or the cyclic GMP concentrations in the cerebral cortex and hippocampus. Thus, increased noradrenergic activity during status epilepticus does not seem responsible for lipolysis or for activation of guanylate cyclase. 相似文献
33.
Zbyněk Likovský Jaroslava Grimová Antonín Dlabač Jan Hondlík Karel Smetana 《Naunyn-Schmiedeberg's archives of pharmacology》1973,276(2):181-186
Summary The incidence of diverse types of nucleoli in peripheral blood lymphocytes was established in albino rats with adjuvant-induced disease, either untreated or receiving trimethazone, phenylbutazone, indometacin, or 6-mercaptopurine. Apart from typical clinical symptoms, the adjuvant-induced disease was characterized by an increase in the number of active nucleoli in the lymphocytes present in the peripheral blood of the diseased animals. This increase was influenced by the administration of any of the drugs enumerated. 相似文献
34.
Jaroslava Folbergrová 《Experimental neurology》1997,145(2):442-450
Seizures were induced in immature 18-day-old rats by i.p. administration of homocysteine (11 mmol/kg) and the effects of selected antagonists of NMDA receptors [MK-801 (0.5 mg/kg), AP7 (0.33 mmol/kg), CGP 40116 (10 mg/kg)] and non-NMDA receptors [GDEE (4 mmol/kg), NBQX (two doses, 30 mg/kg each)] were studied. The effect of MgSO4(two doses, 2 mmol/kg each) was also tested. The anticonvulsant effect was evaluated not only from the behavioral manifestations of seizures, but also in terms of some indicators of brain energy metabolism. Rat pups were sacrificed during generalized clonic-tonic seizures, corresponding to 16–45 min after homocysteine administration. Comparable time intervals were used for sacrificing the pups which had received the protective drugs. In contrast to neonatal rats, in which only NMDA antagonists could prevent homocysteine-induced seizures, both NMDA and non-NMDA receptor antagonists exerted an anticonvulsant effect in 18-day-old rats. In addition, the pronounced anticonvulsant effect could be achieved by the combined treatment with low subthreshold doses of NMDA (MK-801) and non-NMDA (NBQX) receptor antagonists. The protection was evident not only in suppressing behavioral symptoms of seizures, but also in preventing most of the metabolic changes accompanying seizures, mainly glycogen degradation. More than a sevenfold accumulation of lactate occurring during seizures was markedly reduced by all the tested drugs, but was not completely eliminated. All antagonists, when given alone in the same doses as those used for seizure protection, remained without any effect on lactate levels. Comparison of the present data with previous findings concerning neonatal rats suggests that there may be a developmental change in anticonvulsant efficacy of non-NMDA receptor antagonists against homocysteine-induced seizures in rats. 相似文献
35.
McBriar MD Guzik H Shapiro S Paruchova J Xu R Palani A Clader JW Cox K Greenlee WJ Hawes BE Kowalski TJ O'neill K Spar BD Weig B Weston DJ Farley C Cook J 《Journal of medicinal chemistry》2006,49(7):2294-2310
Melanin-concentrating hormone (MCH) is a cyclic, nonadecapeptide expressed in the CNS of all vertebrates that regulates feeding behavior and energy homeostasis via interaction with the central melanocortin system. Regulation of this interaction results in modulation of food intake and body weight gain, demonstrating significant therapeutic potential for the treatment of obesity. The MCH-1 receptor (MCH-R1) has been identified as a key target in MCH regulation, as small molecule antagonists of MCH-R1 have demonstrated activity in vivo. Herein, we document our research in a bicyclo[3.1.0]hexyl urea series with particular emphasis on structure-activity relationships and optimization of receptor occupancy, measured both in vitro and via an ex vivo binding assay following an oral dosing regimen. Several compounds have been tested in vivo and exhibit oral efficacy in relevant acute rodent feeding models. In particular, 24u has proven efficacious in chronic rodent models of obesity, showing a statistically significant reduction in food intake and body weight over a 28 day study. 相似文献
36.
This study compares cemented and uncemented total hip arthroplasties performed through either a standard or mini incision. The parameters evaluated were dislocation rates, Gruen and DeLee zones, Barrack cement grading, component positioning, and heterotopic bone levels. There were no statistically significant differences found between the mini and standard incision groups except in 2 parameters. Analysis of femoral stems not in neutral position revealed statistically significant differences between cemented and uncemented stems. The mean anteversion of the mini incision cup was also significantly less than the standard group, although probably not clinically significant. In conclusion, the mini incision does not compromise total hip arthroplasty results on the acetabular side, but varus positioning of the cemented femoral component nearing 2 degrees is concerning for the long-term success of these arthroplasties. 相似文献
37.
Sustained, generalized seizure activity was induced in anaesthetized (70%N2O), paralyzed and artificially ventilated rats by i.p.dl-homocysteine thiolactone in a dose of 11 mmol/kg. Epileptic discharges in the EEG were accompanied by marked perturbation of tissue metabolites. There was a fall in phosphocreatine concentration to 40% of control but only moderate changes in adenine nucleotides, a marked rise in lactate concentration, and a pronounced increase in the lactate/pyruvate ratio. Excessive amounts of dihydroxyacetone phosphate (and glyceraldehyde phosphate) accumulated, indicating that depletion of NAD+ occurred. There was marked accumulation of ammonia, glutamine and alanine, and reduction in glutamate and aspartate concentrations.Administration of a subconvulsive dose of homocysteine (7.5 mmol/kg) gave rise to changes in ammonia and amino acids, qualitatively similar to those occuring during seizures. It is concluded that although changes in the metabolites of the energy reserve were mainly caused by the induced seizures, those affecting amino acid concentrations were significantly influenced by accumulation of ammonia, secondary to metabolism of injected homocysteine.Cerebral blood flow (CBF) and oxygen utilization (CMRO2) were measured during sustained seizures. CMRO2 rose to 150% of control, with a corresponding increase in CBF. 相似文献
38.
McBriar MD Guzik H Xu R Paruchova J Li S Palani A Clader JW Greenlee WJ Hawes BE Kowalski TJ O'Neill K Spar B Weig B 《Journal of medicinal chemistry》2005,48(7):2274-2277
Melanin concentrating hormone (MCH) is involved in regulation of food intake and energy homeostasis. Antagonists of the MCH receptor are expected to affect food intake and weight gain, making MCH-R1 an attractive target for obesity treatment. Herein, we report the discovery of a novel, orally active series of MCH-R1 antagonists that exhibit in vivo efficacy in rodent obesity models. 相似文献
39.
Durcova-Hills G Hajkova P Sullivan S Barton S Surani MA McLaren A 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(30):11184-11188
Germ cells in XY male mice establish site-specific methylation on imprinted genes during spermatogenesis, whereas germ cells in XX females establish their imprints in growing oocytes. We showed previously that in vitro, sex-specific methylation patterns of pluripotent stem cell lines derived from germ cells were influenced more by the sex chromosome constitution of the cells themselves than by the gender of the embryo from which they had been derived. To see whether the same situation would prevail in vivo, we have now determined the methylation status of H19 expressed from the maternal allele, and the expression and methylation status of a paternally expressed gene Peg3, in germ cells from sex-reversed and control embryos. For these imprinted genes, we conclude that the female imprint is a response of the germ cells to undergoing oogenesis, rather than to their XX chromosome constitution. Similarly, both our XY and our sex-reversed XX male germ cells clearly showed a male rather than a female pattern of DNA methylation; here, however, the sex chromosome constitution had a significant effect, with XX male germ cells less methylated than the XY controls. 相似文献
40.
Jaroslava Švarc-Gajić Zorica Stojanović Ivana Vasiljević Isidora Kecojević 《Yao wu shi pin fen xi = Journal of food and drug analysis.》2013,21(4):384-389
Fluorides are common ingredients in pharmaceutical products for oral hygiene due to their recognized effect in the prevention of tooth decay. In dental products, fluorides can be added in several different forms, such as sodium fluoride, sodium monofluorophosphate, tin fluoride, or in the form of different amines. This work describes potentiometric determination of fluorides in the samples of toothpastes and mouthwash. The method was optimized for the particular analytical purpose; namely, for the analysis of toothpastes and mouthwash by applying different sample preparation protocols depending on the fluoride source. Good recovery (93–103%) confirmed the correctness of the sample preparation procedures. Calculated limit of detection and limit of quantification for the optimized method were 1 × 10?3 mg/L and 2.8 × 10?3 mg/L fluoride, respectively. In the minority of the analyzed samples, calculated contents agreed well with the certified values, whereas the samples of mouthwash demonstrated better agreement. 相似文献