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91.
The effects of various metabolically-stable analogs of adenosine on the threshold for seizures in rats was determined by measuring the dose of pentylenetetrazol (PTZ), infused through a tail vein, required to elicit a myoclonic jerk. The adenosine receptor agonists, 2-chloroadenosine (2-ClAdo), cyclohexyladenosine (CHA) and L- and D-phenylisopropyladenosine (L- and D-PIA), all produced dose-dependent elevations of the seizure threshold for pentylenetetrazol in rats. L-Phenylisopropyl-adenosine was the most potent analog of adenosine tested with a dose as small as 5 micrograms/kg (i.v.) producing a 23% increase in seizure threshold for pentylenetetrazol. The rank order of the potency of adenosine agonists in increasing the seizure threshold was L-PIA greater than 2-ClAdo greater than CHA greater than D-PIA, with L-PIA being 79 times more potent than D-PIA. In contrast to these effects, the adenosine receptor antagonist, theophylline, elicited a proconvulsant effect in doses from 15 to 60 mg/kg (i.p.). The effect of theophylline in reducing seizure threshold for pentylenetetrazol peaked at 30 mg/kg, a dose which reduced the seizure threshold by approx. 27%. Support for the involvement of recognition sites for adenosine in the observed modulation of seizure threshold was provided by the antagonism of the elevation of the seizure threshold for pentylenetetrazol induced by 2-ClAdo, by pretreatment with theophylline (5 mg/kg, i.v.). These findings provide support for the idea that endogenous adenosine may function as a regulator of seizure susceptibility. 相似文献
92.
K. Selvig 《European journal of clinical pharmacology》1981,19(2):149-155
Summary Serum concentrations and urinary excretion of proxyphylline have been measured in five healthy adults after intravenous (29 µmol/kg), single oral (21 µmol/kg) and multiple oral (21 µmol/kg three times a day) doses to produce steady state. The mean peak time after oral administration was 29 min. The mean fraction absorbed was 1.09 calculated from serum concentrations, and 1.05 calculated from urinary excretion of the drug. The apparent volume of distribution was 0.61 l/kg (0.53–0.72 l/kg), 26% higher in males than in females. A two-compartment open model was found to describe the decline in the serum concentrations, giving a mean distribution half-life of 6 min. The intersubject ranges of biological half-life were 8.1–12.1 h and 8.3–12.6 h calculated from serum and urine data, respectively. 24% (18–29%) of the dose was excreted unchanged in urine, which agreed with the relationship between the calculated total body clearance and the renal clearance of the drug.Fellow of the Norwegian Research Council for Science and the Humanities 相似文献
93.
Summary The relation between plasma concentration of theophylline and number of apnea in preterm infants was studied in six patients. The apnea frequency was monitored after cessation of theophylline treatment and plotted against the log plasma concentration of theophylline. It was calculated that at an average plasma concentration of 40 µmol/l (7.25 µg/ml) the preterm infants had two or less apnea per 12 h. On the basis of our results we suggest that 40 µmol/l is the minimum plasma concentration of theophylline for optimal effect on apnea in preterm infants.Supported by the Swedish Medical Research Council (19X-05234 04X-04496), Expressen's Prenatal Research Foundation, Stiftelsen Samariten and Swedish Society of Medical SciencesPresented at the International Workshop on Perinatal and Pediatric Aspects of Clinical Pharmacology, Heidelberg, Federal Republic of Germany, 27–29 February 1980 相似文献
94.
Effect of Theophylline on the Proportion and Function of T-Suppressor Cells in Asthmatic Children 总被引:1,自引:0,他引:1
T-cell subpopulations and their function were studied in asthmatic children with or without theophylline therapy. A decreased proportion and function of theophylline-sensitive T-suppressor cells was found in fresh peripheral blood of asthmatic children. Following peripheral blood mononuclear cells (PBMC) incubation in theophylline-free medium, the proportion of theophylline-sensitive T-cells in asthmatic children treated with theophylline was elevated to normal values. However, their suppressive effect on control lymphocyte proliferation was unchanged. 相似文献
95.
M. Sano K. Kawakatsu C. Ohkita I. Yamamoto M. Takeyama H. Yamashina M. Goto 《European journal of clinical pharmacology》1988,35(2):161-165
Summary The effect of three new fluoroquinolones on theophylline kinetics and the urinary excretion of metabolites was studied in 5 healthy subjects (3 male, 2 female).All subjects received serial, single i.v. infusions of theophylline (aminophylline, 250 mg) over 60 min after 200 mg doses of a quinolone (enoxacin, ofloxacin, norfloxacin) every 8 h for 3 consecutive days, the quinolone being administered up to the day following theophylline administration.Pretreatment with ofloxacin and norfloxacin did not influence theophylline disposition, but theophylline clearance fell from 0.054 to 0.027 l·h–1·kg–1 in the presence of enoxacin, without a change in the apparent volume of distribution. Enoxacin, too, was the sole compound to increase the urinary excretion of theophylline (33.2 vs 43.9 mg, before vs after treatment), and significantly to decrease the excretion of 3-methylxanthine (3-MX), 1-methyluric acid (1-MU) and 1,3-dimethyluric acid (1,3-DMU) in 24-h urine samples (from 19.8 to 7.16 mg, from 28.3 to 10.3 mg and from 68.8 to 49.5 mg, respectively). The effect of the quinolones on hepatic drug metabolizing enzyme activity was investigated in each subject using the ratios of 6-hydroxycortisol to total 17-hydroxycorticosteroids and to free cortisol in 24-h urines as an index of the hepatic P-450-dependent enzyme system. No significant difference in ratio was observed between control and other treatments. It is concluded that the theophylline-enoxacin interaction was largely due to inhibition of a metabolic system other than the common hepatic P-450 system. 相似文献
96.
W. Boehning 《European journal of clinical pharmacology》1990,38(1):43-45
Summary Thirty adults with chronic obstructive airways disease, who were stabilised on theophylline and corticosteroids, took part in a single blind study of the effects of cimetidine and ranitidine on plasma theophylline concentrations. The patients were randomised to receive either 150 mg ranitidine b. d. or 400 mg cimetidine b. d. for one week and serial plasma theophylline measurements were made over a 12-hour period on two consecutive days before, during and after treatment with the H2-antagonist.There was a significant increase in plasma theophylline during treatment with cimetidine; two patients had levels > 20 mg·1–1. The average increase in the theophylline concentration due to cimetidine was 32%. There was no significant change in plasma theophylline during ranitidine administration. No adverse effect occurred in any patient during the study. 相似文献
97.
S. H. D. Jackson J. K. Wiffen A. Johnston C. A. Peverel-Cooper 《European journal of clinical pharmacology》1984,26(5):635-637
Summary Six healthy volunteers received an iv infusion of 317 mg lysine theophylline (equivalent to 197 mg anhydrous theophylline) in order to calculate theophylline clearance by standard methods. They subsequently received a 20 minute inhalation of nebulised lysine theophylline. Serum and salivary theophylline concentrations were measured and all saliva was collected for the first hour. From these concentrations estimates were made of the distribution of theophylline into the blood and saliva with 40% to 94% identified in the blood. Very high salivary concentrations were reached during the inhalation phase with saliva: serum concentration ratios of between 60 and 1600. 相似文献
98.
M. I. Lucena J. Almagro F. Rius F. Sanchez de la Cuesta 《European journal of clinical pharmacology》1988,35(6):669-671
Summary Sustained-release theophylline 10.1 mg/kg b.d. was given with placebo or fenoterol 2.5 mg t.d.s. to 12 patients with chronic airway obstruction.Fenoterol did not significantly affect the steady-state serum theophylline trough level (11.84 µg/ml for fenoterol vs 11.10 µg/ml for placebo). Addition of fenoterol produced no further increase in spirometric function nor in clinical status. 相似文献
99.
40 ventilated premature infants, with gestational ages of 24-34 weeks and a mean birthweight of 1422 g, were entered into a randomised controlled trial. 20 of the infants received orally 5 mg/ml anhydrous theophylline dissolved in 20% pure alcohol, with a loading dose of 5 mg/kg and then 1.25 mg/kg every 6 h. Plasma samples were assayed via an emit enzyme immunoassay, demonstrating satisfactory serum levels in all infants at 54 h after the loading dose. Possible side-effects were seen only in two infants, in one a tachycardia (220 beats/min) and the other became agitated during treatment. 相似文献
100.