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61.
Effect of Felbamate on Phenytoin and Carbamazepine Serum Concentrations 总被引:13,自引:13,他引:0
Felbamate (FBM) is a novel antiepileptic drug (AED) undergoing clinical trials in the United States. During a double-blind, cross-over clinical trial, patients received concomitant phenytoin (PHT) and carbamazepine (CBZ). Dosages of PHT and CBZ were adjusted to maintain serum concentrations +/- 20 and +/- 25% of baseline values. All patients required a PHT dosage decrease of 10-30% during active FBM treatment to maintain stable concentrations. CBZ serum concentrations decreased significantly in patients receiving active FBM. The mean decrease was 1.3 micrograms/ml and occurred in 30 of 32 patients. Therefore, FBM apparently causes a bidirectional effect on the serum concentrations of PHT and CBZ when all three drugs are taken concomitantly. 相似文献
62.
A 67-year-old man developed a sudden onset of severe isolated thrombocytopenia (platelet count, 1000/mm3) after 10 days of phenytoin administration as a prophylactic measure prior to craniotomy. The patient had also been taking cimetidine for 2 months prior to admission. No other hematological complications were noted, and an extensive hematologic investigation was otherwise unremarkable. Rapid resolution of the thrombocytopenia upon discontinuation of phenytoin and cimetidine strongly suggests a drug-induced adverse reaction. 相似文献
63.
参照美国药典收载的“延效苯妥英钠胶囊”的体外释放速率,筛选处方,制成苯妥英钠缓释片,并进行体外释放度测定。根据测定结果表明,能达到延效目的,因此,每天只需服药1~2次。 相似文献
64.
Male albino rats were injected with 25 mg/kg of phenytoin (PHT) every day for 20 consecutive days and were tested on days 21 and 28 for their response to 1 or 2 mg/kg of muscimol, a GABA receptor agonist. Rats treated with PHT showed a decreased responsiveness to muscimol-induced catalepsy (2 mg/kg) on day 21 but not on day 28. Acutely administered PHT, on the contrary, had a tendency to potentiate muscimol-induced catalepsy. Muscimol-induced catalepsy was not antagonized by acute treatment with bicuculline (0.5–2.0 mg/kg). It is proposed that withdrawal after long-term administration of PHT reduces the sensitivity of a GABA receptor site not sensitive to bicuculline. 相似文献
65.
Interactions of Phenytoin and Phenobarbital in Terms of Order and Temporal Spacing of Administration in Monkeys 总被引:3,自引:3,他引:0
The present study investigated order and temporal spacing interactions of phenytoin and phenobarbital in terms of plasma levels during multiple dosing in monkeys. Phenytoin at a dose of 30 mg/kg and phenobarbital at a dose of 3 mg/kg were administered separately to 4 animals (control group) by nasogastric intubution daily for 10 days. In four subsequent 10-day periods the drugs were administered together in 4 other animals (interaction group) at different times of the day (immediately following one another, 1/2 hr apart, and 6 hr apart) and in a different order of administration (either phenobarbital first and phenytoin later, or the reverse). Blood samples were obtained on the 5th, 8th, and 10th day of each 10-day period. The plasma data indicated: (a) phenytoin is capable of autoinduction, (b) phenobarbital lowers the levels of phenytoin under the four methods of administration studied here, and (c) phenytoin can affect the levels of phenobarbital. The latter interaction is a function of order and temporal spacing of drug administration. 相似文献
66.
The effect of phenytoin (PHT) on serum folate and the effect of additional oral folic acid (FA) on serum folate during continued treatment with PHT were studied in 13 healthy male subjects 20-35 years of age. The study was divided into two phases: Phase I determined Vmax (mg/kg/day) and Km (microgram/ml) of PHT in order to calculate the PHT doses needed for the second phase. Phase II was a four-way cross-over study to examine the effect of 1 and 5 mg FA on total serum PHT concentrations 1 microgram/ml less and 5 micrograms/ml greater than the subject's Km, Km-1 and Km+5, respectively. Both phases examined the effect of PHT on serum folate. In Phase I, serum folate decreased by a mean and standard deviation of 42.15 +/- 21.44% after an average of 24.15 +/- 5.63 days of PHT administration, with a mean steady-state total serum PHT concentration of 8.45 +/- 2.70 micrograms/ml. Mean percentage decreases in serum folate before the addition of 1 and 5 mg FA in Phase II were 12.80 +/- 31.45% and 23.24 +/- 21.24% for Km-1 and Km+5, respectively. The average numbers of days of PHT administration and total serum PHT concentrations before FA administration were 9.52 +/- 3.34 and 15.84 +/- 7.02 days, and 2.60 +/- 2.18 and 8.64 +/- 3.44 micrograms/ml, for Km-1 and Km+5, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
67.
I. Jurna 《Naunyn-Schmiedeberg's archives of pharmacology》1968,260(1):80-88
Summary The effect of metamphetamine, propylhexedrine and biperiden on reserpine rigidity in the rat was assessed in an electromyographical study. For comparison the anticonvulsant agent phenytoin was also included in the investigation. Tonic electromyographical activity during stretch of the calf muscles served as an indicator of rigidity. All drugs tested and their combinations depressed the rigidity elicited by an intravenous injection of a high dose of reserpine.Supported by a grant of the Deutsche Forschungsgemeinschaft. 相似文献
68.
Summary The effects of amphetamine, metamphetamine, propylhexedrine, biperiden and atropine were studied in experiments on electroseizure threshold in rats. In high doses these drugs lowered the threshold of electroseizures and antagonized the threshold lowering produced by reserpine, with the exception of atropine, which enhanced the action of reserpine. Low doses of the drugs and combinations of low doses of metamphetamine, propylhexedrine and biperiden did not influence electroseizure threshold, but inhibited the action of reserpine. The effect of phenytoin on the threshold lowered by reserpine was enhanced by low doses of metamphetamine, propylhexedrine and biperiden. Tetrabenazine caused threshold lowering which was antagonized by metamphetamine, propylhexedrine, biperiden and atropine. Pretreatment with -methyl-p-tyrosine, but not with diethyldithiocarbaminate abolished the effect of high doses of metamphetamine or propylhexedrine on the electroseizure threshold. Inhibition of the formation of DOPA or noradrenaline did not influence the action of reserpine or the antagonism between reserpine and the drugs of the amphetamine group. After a repeated injection of metamphetamine tachyphylaxis developed.Supported by a grant of the Deutsche Forschungsgemeinschaft. 相似文献
69.
Since glutathione is thought to be involved in cerebral functions, changes in the glutathione level imply modulations of the neurotransmission in addition to all the known effects of GSH. It was investigated whether alterations of the cerebral glutathione can be induced by consumption of GSH, by inhibition or stimulation of the synthesis of GSH, or by an inhibition of the re-reduction of the oxidized glutathione. Aminophenazone, propyphenazone, acetaminophen, phenytoin, morphine and nitrofurantoin, known to deplete hepatic GSH, had no effects on cerebral GSH. Diethyl maleate (0.6 ml/kg) decreased the cerebral content of GSH and GSSG in adult rats as well as in fetuses. The depletion of the cerebral GSH caused by diethyl maleate treatment for 4 days was followed by an increase up to 125% and a subsequent return to the normal level after 1 week. In rats starved up to 71 h deficiency of exogenous amino acids caused only a minimal or no decrease in cerebral GSH. The specific inhibitor of the gamma-glutamylcysteine synthetase BSO only depleted GSH in the brain of young mice following the repeated s. c. administration of a high dose (890 mg/kg). After cobaltous chloride (20 mg/kg; twice a day for 2 or 4 days) the GSH level in the brain was unchanged. In vivo inhibition of the cerebral glutathione reductase was caused by ammonium metavanadate (12.5 mg/kg; three times a week for 6 weeks). Nitrofurantoin (150 mg/kg) had no effect. After lomustine (10 mg/kg) a minimal increase in glutathione reductase was found, but simultaneously also an increase in GSSG and of the ratio GSSG/total glutathione. 相似文献
70.
Total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein cholesterol, apolipoproteins A, A1, and B and gamma-glutamyltransferase (ggt) serum concentrations were measured in 100 adult epileptic patients receiving chronic phenytoin (PHT) treatment and in 100 control subjects. In relation to controls, patients showed higher HDL cholesterol, apolipoproteins A and A1, and ggt levels and lower LDL cholesterol and apolipoprotein B values; the significance of the results was greater in women than in men. Among patients, ggt levels were positively correlated with PHT plasma concentrations; likewise, a negative correlation was found between the apolipoprotein A/A1 ratio and the PHT and ggt plasma levels, and a positive correlation between the apolipoprotein A/A1 ratio and the LDL/HDL cholesterol ratio. These data indicate that PHT exerts a beneficial effect on the serum lipids profile. 相似文献