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Summary The kinetics of a single 5-mg oral dose of the thienodiazepine clotiazepam was evaluated in a series of patients with biopsy-proven cirrhosis, and in patients with renal insufficiency requiring maintenance hemodialysis, compared to healthy matched controls. Clotiazepam volume of distribution (Vz) was significantly smaller in cirrhotic patients than in controls (1.83 vs 2.57 l/kg), and total clearance was likewise reduced (2.15 vs 3.15 ml/min/kg). Elimination half-life was similar between groups (10.0 vs. 10.2h). There were no significant differences between renal failure and control patients in clotiazepam Vz, oral clearance, or elimination half-life. Thus cirrhosis is associated with reduced clearance of clotiazepam, probably due to impairment of its microsomal oxidation. However clotiazepam disposition is not significantly altered in dialysis-dependent renal insufficiency patients.Supported in part by Grant OC 10/6–4 from Deutsche Forschungsgemeinschaft, and Grant MH-34223 from the United States Public Health Service. 相似文献
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Differential effects of chronic lorazepam and alprazolam on benzodiazepine binding and GABAA-receptor function. 下载免费PDF全文
W. R. Galpern L. G. Miller D. J. Greenblatt R. I. Shader 《British journal of pharmacology》1990,101(4):839-842
1. Chronic benzodiazepine administration has been associated with tolerance and with downregulation of gamma-aminobutyric acidA (GABAA)-receptor binding and function. However, effects of individual benzodiazepines on brain regions have varied. 2. To compare the effects of chronic lorazepam and alprazolam, we have administered these drugs to mice for 1 and 7 days (2 mg kg-1 day-1) and determined benzodiazepine receptor binding in vivo with and without administration of CL 218,872, 25 mg kg-1 i.p., and GABA-dependent chloride uptake in 3 brain regions at these time points. 3. Benzodiazepine binding was decreased in the cortex and hippocampus at day 7 compared to day 1 of lorazepam, with an increase in CL 218,872-resistant (Type 2) sites in both regions. Maximal GABA-dependent chloride uptake was also decreased in the cortex and hippocampus at day 7. 4. Binding was decreased only in the cortex after 7 days of alprazolam, with no significant change in Type 2 binding. Maximal GABA-dependent chloride uptake was also decreased only in the cortex. 5. These data suggest that the effects of chronic benzodiazepine administration on the GABAA-receptor may be both region-specific and receptor subtype-specific. 相似文献
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Periosteal Ewing sarcoma 总被引:3,自引:0,他引:3
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Sensitivity to triazolam in the elderly 总被引:8,自引:0,他引:8
D J Greenblatt J S Harmatz L Shapiro N Engelhardt T A Gouthro R I Shader 《The New England journal of medicine》1991,324(24):1691-1698
BACKGROUND. Elderly persons frequently appear to be sensitive to the effects of many drugs that depress the central nervous system. We studied the effect of age on the pharmacokinetics and pharmacodynamics of the benzodiazepine hypnotic agent triazolam, now the most frequently prescribed hypnotic drug in the United States. METHODS. Twenty-six healthy young subjects (mean age, 30 years) and 21 healthy elderly subjects (mean age, 69 years) participated in a four-way crossover study. After a single-blind adaptation trial with placebo, each subject received, in random order and in double-blind fashion, single doses of placebo, 0.125 mg of triazolam, and 0.25 mg of triazolam. For 24 hours after the administration of each of the three study medications, plasma triazolam levels were determined and psychomotor performance, memory, and degree of sedation were assessed. RESULTS. Plasma triazolam concentrations increased in proportion to the dose, but the elderly subjects had higher plasma concentrations due to reduced clearance of the drug. The degree of sedation as rated by an observer and the reduction in the subjects' performance on the digit-symbol substitution test were both greater in the elderly than in the young subjects after they were given the same doses. The relation of the plasma triazolam concentration to the degree of impairment was similar for the two groups. As part of the study, information was presented 1 1/2 hours after the administration of the drugs; the subjects' ability to recall the information 24 hours later was impaired by both doses of triazolam, and the percent decrease was similar in the young and elderly groups. CONCLUSIONS. Triazolam caused a greater degree of sedation and greater impairment of psychomotor performance in healthy elderly persons than in young persons who received the same dose. These effects resulted from reduced clearance and higher plasma concentrations of triazolam rather than from an increased intrinsic sensitivity to the drug. On the basis of these results, the dosage of triazolam for elderly persons should be reduced on average by 50 percent. 相似文献
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In a prospective, randomized study of insemination with donor semen,
intracervical insemination by straw was compared with insemination using a
cervical cap with an intracervical reservoir. A total of 91 patients
completed 486 treatment cycles. There were no significant differences in
age, parity, indication for insemination by donor, or method of cycle
monitoring between women who became pregnant and those who did not conceive
with either insemination method. In 236 standard intracervical insemination
cycles, 14 patients became pregnant (5.9% per cycle), whereas 38 patients
conceived in 250 cervical cap cycles (15.2% per cycle). Both the crude
pregnancy rates and the cumulative pregnancy rates calculated by the
Kaplan-Meier life-table method were significantly different (chi(2)-test, P
< 0.001, and log-rank test, P < 0.005 respectively). Pregnancy rates
in artificial insemination with cryopreserved donor semen may be improved
by the use of a cervical cap when compared to cervical insemination by
straw. The use of the cervical cap may prolong the exposure of the
spermatozoa to the cervical mucus and prevent the backflow of semen into
the vagina.
相似文献