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71.
Diazepam effects on the performance of healthy subjects are not enhanced by treatment with the antihistamine ebastine.
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1. We have given 12 healthy subjects the H1-antihistamine ebastine (20 mg) or placebo in a randomized double-blind and crossover study for 1 week each. The subjects were tested for drug effects on day 6 of each period, and for interactions of ebastine with oral 15 mg diazepam (DZ) on day 7. On both days, the testing runs were at baseline and 1.5, 3, 4.5 and 6 h after intake. 2. The performance was evaluated both objectively (digit symbol substitution, flicker fusion, Maddox wing, simulated driving, body balance) and subjectively (visual analogue scales, questionnaires). Venous blood was sampled daily during the maintenance and during each testing round for the assay of plasma carebastine (the active metabolite of ebastine) by high pressure liquid chromatography and plasma diazepam by radioreceptor assay. Three-way ANOVA, paired t-test, Wilcoxon rank sign test and Fisher's fourfold table test were used for data analysis. 3. Plasma carebastine reached steady levels from day 3 onwards. The mean concentrations in the morning were 82 micrograms l-1 on day 6 and 85 micrograms l-1 on day 7. The rise (+ 150%) in plasma carebastine after an extra 20 mg ebastine was not modified by DZ. Ebastine did not affect performance objectively or subjectively, yet borderline drowsiness was recorded during the first 3 h. On day 7, plasma DZ concentrations peaked (mean 480 micrograms l-1) at 1.5 h after the intake. DZ produced impaired performance in various objective tests, and drowsiness, weakness, clumsiness, mental slowness and poor performance were reported on visual analogue scales.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
72.
M. J. Mattila A. Patat T. Seppälä H. Kalska M.-L. Jalava J. Vanakoski C. Lavanant 《European journal of clinical pharmacology》1996,51(2):161-166
Objectives: Amisulpride is a benzamide antipsychotic that binds selectively to dopamine D2- and D3-receptors, preferentially in limbic and hippocampal structures. Since other substituted benzamides have a limited or negligible
interaction with alcohol on human performance, amisulpride was studied for this potential.
Methods:
In a randomised double-blind crossover study, 18 young, non-smoking men took single oral doses of placebo and amisulpride
50 mg and 200 mg, without and with ethanol (0.8 g ⋅kg−1) taken 30 min later. Objective performance tests and self-ratings were done at baseline and 1.5, 3.5 and 6.5 h after drug
intake. Memory (immediate and delayed recall) was tested 2 h after dosing. Breath ethanol and the plasma concentrations of
amisulpride and prolactin were measured. Three-way ANOVA + Newman-Keul tests were used for statistical analyses; interactions
were confirmed by factorial contrast ANOVA.
Results:
Mean blood ethanol was 0.94, 0.62 and 0.26 g ⋅l−1 at the three test times. It produced significant impairment in all performance tests (symbol digit substitution, simulated
driving, body sway, flicker fusion, tapping, nystagmus), reduced both immediate and delayed recall in memory tests, and caused
subjective clumsiness, muzziness and mental slowness, mainly between 1.5 to 4.5 h after dosing. Amisulpride, 50 and 200 mg
elevated plasma prolactin but had minimal or no effect on performance, attention and memory. The decreases in immediate free
recall after the 50 mg dose and in delayed free recall after the 200 mg dose were slight. Amisulpride neither modified blood
ethanol concentrations nor enhanced the detrimental effect of ethanol on skilled and cognitive performance; it slightly antagonised
ethanol in the digit copying test. Ethanol did not modify the effect of amisulpride on plasma prolactin, and the plasma concentrations
of amisulpride were little changed by ethanol.
Conclusions:
Amisulpride in single oral doses of 50 and 200 mg did not interact significantly with the effects of high, moderate or low
concentrations of ethanol on human skilled and cognitive performance. The drugs did interact pharmacokinetically.
Received: 22 December 1995/Accepted in revised form: 1 April 1996 相似文献
73.
74.
The effect of GABA on basal and stimulated TSH secretion was studied in male rats. The effects of drugs on basal TSH levels were not consistent. Muscimol(0.5 mg/kg subcutaneously, but not 2 mg/kg) increased whereas baclofen (10 mg/kg intraperitoneally), amino-oxyacetic acid (AOAA, 20 mg/kg intraperitoneally) and bicuculline (2 mg/kg intraperitoneally, but not 1 or 4 mg/kg) decreased basal TSH concentrations. Muscimol, AOAA and baclofen dose-dependently reversed the TSH cold-response, as did a large dose of di-n-propylacetate (DPA, 400 mg/kg intraperitoneally) and 500 mg/kg (but not 50, 100 or 1500 mg/kg intraperitoneally) of GABA itself. Bicuculline was not effective alone. Neither did it modify the effects of muscimol, AOAA and GABA on the cold-stimulated TSH response. None of the drugs studied (AOAA, GABA, bicuculline) modified TRH-induced (100 ng intraperitoneally) TSH-response. GABA injected into the third ventricle (5-50 microgram/rat) or into the medial basal hypothalamus (MBH, 5 microgram/rat) had no effect on the basal TSH levels. However, the TSH cold-response was inhibited when GABA (5 microgram/rat) was infused into the MBH but not when it was infused into the third ventricle (5-50 microgram/rat). The results suggest that GABAergic pathways may have an inhibitory effect on the stimulated TSH secretion in male rats. The locus of this inhibition is not situated in the anterior pituitary, but possibly in the MBH. 相似文献
75.
K. Virtanen J. S. Salonen M. Scheinin E. Iisalo V. Mattila 《Basic & clinical pharmacology & toxicology》1980,47(4):274-278
Abstract: A simple and sensitive radioimmunoassay (RIA) for the determination of doxepin and desmethyldoxepin in plasma or serum has been developed using a previously reported antiserum to the tricyclic anti-depressants. Before assay, doxepin is separated from desmethyldoxepin with selective extraction at different pH values enabling each to be measured specifically. 3H-imipramine is used as tracer. By using the extraction procedure doxepin and desmethyldoxepin concentrations can be measured down to 9 nmol/l from a 0.1 ml sample. If necessary, sensitivity can be doubled by taking a 0.2 ml sample to the extraction. Recoveries of doxepin and desmethyldoxepin were quantitative when the drugs were added at different concentrations to normal, pooled human plasma and the inter- and intra-assay coefficients of variation did not exceed 9%. The concentrations obtained from patient samples by the present RIA correlated well with those by high-pressure liquid chromatography. The RIA was also shown to be useful in pharmacokinetic single dose studies with doxepin. 相似文献
76.
77.
78.
A series of 25 surgically treated patients with the Morgagni type of diaphragmatic hernia is presented. Twenty-two of the patients were female and three were male. The hernia was on the right side in all of them. Five of the patients had symptoms which were predominantly gastrointestinal. The remainder of the patients were asymptomatic and were admitted to hospital because of an abnormal finding at chest X-ray. All but one were operated transthoracically. In one case an abdominal approach was used because cholecystectomy was performed simultaneously with the hernial repair. In 3 cases the hernail sac contained a portion of transverse colon and in 9 cases, omentum. In 12 there was an accumulation of adipose tissue in the hernial sac, and in 2 cases it was empty when operated. There were no serious complications and no mortalities. 相似文献
79.
Xylitol has been suggested as a more advantageous calory source for intravenous administration than glucose in certain clinical situation, but the general suitability of intravenous xylitol infusion has not been confirmed. Thirty-middle-aged women were infused with 100 g of xylitol as postoperative fluid therapy after gynaecological laparotomy and general anaesthesia. Another 10 women received 50 g of glucose in a similar manner and served as a reference group. Infusion of xylitol both at the rate of 0.25 g/kg/h (1000 ml 10% xylitol in approx. 8 h) and 0.5 g/kg/h (1000 ml 10% xylitol in approx. 4 h) caused a distinct increase in the serum concentrations of lactic acid, pyruvic acid, and uric acid; such an increase was not seen with glucose infusion. The faster infusion of xylitol also distinctly increased serum bilirubin concentrations. Because of the possibility of lactic acidosis and urate deposits in kidneys, infusion of 100 g or more of xylitol at a rate of 0.25 g/kg/h or faster is not safe for postoperative fluid therapy in routine clinical work. 相似文献
80.