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991.
Summary A method has been developed for the quantitative determination of heptabarbital [5-(1-cyclohepten-1-yl)-5-ethylbarbituric acid] in human plasma after administration of single therapeutic doses of the drug. It involves a single extraction step followed by gas chromatography with alkali flame ionization detection, and the results were linear in the concentration range 0.125 – 5.0 µg/ml plasma. The pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium were studied in a crossover design in 7 healthy volunteers after oral administration of 20 tablets containing 200 mg heptabarbital and hard gelatine capsules containing an equivalent amount of its sodium salt. Heptabarbital concentrations in plasma were determined at regular intervals. The absorption of heptabarbital from the tablets was quite slow and peak level times varied from 1.5 to 4 h. The sodium salt was absorbed more rapidly and peak concentrations occurred between 1/3 and 2 h. In all cases the elimination of heptabarbital could be described by a single first-order process with an average half-life of 7.6 h (range 6.1 – 11.2 h). The half-life of the drug in each individual was about the same in the two trials. The relative bioavailability in each volunteer was estimated by comparing the areas under the plasma concentration curves. The sodium salt had an average bioavailability of 83% relative to the free acid. In some volunteers urinary excretion of unchanged heptabarbital was measured; cumulative excretion amounted to 0.16 – 0.30% of the administered dose. Four volunteers received one tablet each night for eight or ten days, but no accumulation was found. In three volunteers the half-life of the drug prior to and after these experiments did not change, whereas in the other volunteer the half-life decreased from 7.1 to 4.6 h. The possibility of enzyme induction should be considered when heptabarbital is taken regularly. It was concluded that heptabarbital was a suitable drug for the treatment of insomnia, since its half-life was rather short. Heptabarbital sodium may be used for induction of sleep, whereas Medomin® tablets, i.e. heptabarbital free acid, may be prescribed when the maintenance of sleep is the primary reason for treatment with a hypnotic drug. 相似文献
992.
M. D. Rawlins P. Collste Marianne Frisk-Holmberg Margareta Lind J. Östman F. Sjöqvist 《European journal of clinical pharmacology》1974,7(5):353-356
Summary Plasma concentrations of alprenolol during one inter-dose interval and steady-state plasma concentrations have been determined in 30 patients treated for a prolonged period. The latter varied 25-fold between patients who received identical doses. Peak plasma concentrations were achieved at similar times in different patients, but only the level 5–7 h after administration was well correlated (r=0.997) with the steady-state concentration. The type of pharmacokinetic analysis described here is recommended for studies of the relationships between plasma concentration and effects of drugs with short half-lives. 相似文献
993.
A. Aaes-Jørgensen L. Kirk E. Petersen P. Danneskiold-Samsøe A. Jørgensen 《Psychopharmacology》1983,81(1):68-72
Cis(Z)-clopenthixol decanoate in Viscoleo (Sordinol® Depot, Cisordinol® Depot, Clopixol® Inj.) was given intramuscularly to nine schizophrenic patients with dosage intervals of 1 or 2 weeks. Serum concentrations of the two geometric isomers of clopenthixol and its N-dealkyl metabolite were recorded in two successive dosage intervals. Significant correlations were found for dose vs area under the serum concentration curve and vs serum concentrations measured on individual days. The last mentioned concentrations are good measures of the area under the serum concentration curve, which expresses the drug load of the patient. The serum concentration curves in two successive dosage intervals were very similar. Maximum serum concentration was seen 5–7 days after injection and the mean maximum/minimum fluctuation was 1.6 with the 2-week dosage interval. The finding of very low amounts of the trans(E)-isomers of clopenthixol and the N-dealkyl-metabolite shows that isomerization of the cis(Z)-compounds into the corresponding trans(E)-isomers does not take place within the organism. 相似文献
994.
G. Esposito A. Faelli M. Tosco V. Capraro 《Pflügers Archiv : European journal of physiology》1981,390(2):202-206
Hyperglycemia produced by intravenous infusion of glucose causes, in the everted jejunum of rat, an increase of net transintestinal transport of glucose, Na and water without modifying their cell concentration. The concentration of glucose in the fluid pouring out at the serosal side is higher than the calculated intracellular concentration, especially in the experiments in which the serosal compartment is initially empty. This fact could be explained by the possible existence of an active extrusion mechanism in the basolateral membrane of the enterocyte. 相似文献
995.
Robert N. Carpenter Ian Brown B. Chir Joseph S. Mitchell 《International journal of radiation oncology, biology, physics》1983,9(1):51-55
Uptake studies of the potential endoradiotherapeutic agent, 6-125I-iodo-2-methyl-1,4-naphthoquinoI bis(diammonium phosphate) have been carried out in vitro on a wide range of normal and malignant human cells. In general, for a standardized dose of 0.1 μCi/ml, the uptake of the compound into normal cells was 0.0015–0.135 pCi/cell. Uptake into malignant cells was significantly higher than normal cells; uptakes of 0.89–11.3 pCi/cell were noted for melanoma, teratoma of testis, osteosarcoma and adenocarcinoma of colon and pancreas. Comparative uptake ratios formelanoma: Chang liver cells and testicular terastomamormal testis were 29 and 23, respectively. Larger uptake ratios are usually observed with higher doses. 相似文献
996.
S. Pynnonen J. Kanto M. Sillanp R. Erkkola 《Basic & clinical pharmacology & toxicology》1977,41(3):244-253
Abstract The pharmacokinetics of carbamazepine were studied during pregnancy and early childhood by investigating the extent of its placental penetration and its distribution in the foetal and neonatal tissues at autopsy. In foetuses the liver and kidney contained high levels of carbamazepine, whereas brain and lungs had low values. Carbamazepine-10,11-epoxide was also detected in the foetal circulation. At autopsy material, carbamazepine was localized mostly in the cerebral cortex, heart, liver and kidney. The concentration of carbamazepine in the milk was found to be 60 per cent of the respective plasma value. 相似文献
997.
The levels of taurine in brain, heart, liver, kidney, spleen, muscle, and blood of rabbit were determined during development. Taurine was found to be present in a very high concentration at birth and to decrease during maturation in all parts studied except heart. 相似文献
998.
In a 10 year old boy 8 hours after taking about 16 mg -acetyl-digoxin a maximum serum digoxin level of 31.8 ng/ml was measured radioimmunologically. This is the highest digitalis level in childhood described to date.The serum potassium level rose to 7.4 mmol/l.Complete atrio-ventricular block, and salves of ventricular premature beats were the most serious rhythm disturbances. The absence of life threatening rhythm disturbances is attributed to the early use of diphenylhydantoin in small frequent doses.Supported by the German Research Foundation 相似文献
999.
1000.
Fischer W Franke H Gröger-Arndt H Illes P 《Naunyn-Schmiedeberg's archives of pharmacology》2005,371(6):466-472
ATP, ADPS and UTP induced a comparable rise in the intracellular Ca2+ concentration ([Ca2+]i) in HEK-293 cells using fura-2 microfluorimetry. The responses persisted in Ca2+-free medium, but were abolished following depletion of intracellular Ca2+ stores by cyclopiazonic acid. Cross-desensitisation experiments demonstrated that exposure to ADPS has no marked effect on UTP-induced [Ca2+]i transients and vice versa. Whereas the P2Y1 receptor-selective antagonist 2-deoxy-N6-methyladenosine 3,5-diphosphate (MRS 2179) abolished the responses to ADPS, it decreased and did not alter the responses to ATP and UTP respectively. Although the P2Y1/P2Y4 receptor-preferential antagonist pyridoxalphosphate-6-azophenyl-2,4-disulphonic acid (PPADS) abolished the responses to ADPS, and decreased those to ATP, it also depressed the UTP-induced [Ca2+]i transients. Suramin, an antagonist with preference for P2Y2 receptors decreased both the ATP- and UTP-induced [Ca2+]i reactions. After numerous splittings, HEK-293 cells failed to react to ADPS; however, repeated superfusion with this P2Y1 receptor agonist restored the [Ca2+]i signals. In agreement with the functional data, real-time polymerase chain reaction and immunocytochemical studies indicated the presence of P2Y1, P2Y2 and P2Y4 receptors. Our findings raise doubt with respect to the reliability of HEK-293 cells as expression systems for recombinant P2X receptors, because of a possible functional interaction with endogenous P2Y receptors. 相似文献