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31.
Dual mechanisms of regulation of type I iodothyronine 5''-deiodinase in the rat kidney, liver, and thyroid gland. Implications for the treatment of hyperthyroidism with radiographic contrast agents.
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D L St Germain 《The Journal of clinical investigation》1988,81(5):1476-1484
Alterations in thyroid hormone status and the administration of radiographic contrast agents can markedly influence iodothyronine metabolism and, in particular, the activity of type I 5'-deiodinase (5'DI). In the present studies, the mechanisms responsible for these effects have been reassessed. As previously reported, the addition of iopanoic acid (IOP) to broken cell preparations resulted in a competitive pattern of 5'DI inhibition. However, the in vivo administration to rats of IOP or 3,3',5'-triiodothyronine (rT3) resulted in a noncompetitive pattern of inhibition of 5'DI in the liver, kidney, and thyroid gland, whereby marked decreases in maximal enzyme velocity (V max) were noted, with no change in the value of the Michaelis-Menten constant. In rats rendered hyperthyroid by the injection of 3,5,3'-triiodothyronine (T3), 5'DI activity was significantly increased in the liver and the kidney. The administration of IOP to these thyrotoxic animals resulted in a rapid loss of enzyme activity characterized by an approximate 80% decrease in 5'DI V max values in both tissues. Furthermore, this inhibitory effect persisted for longer than 60 h after a single IOP injection. IOP administration also decreased 5'DI V max levels in the thyroid gland by 52%. In other experiments, treatment of intact Reuber FAO hepatoma cells with IOP or rT3 induced a rapid decrease in 5'DI V max levels. In cells treated with cycloheximide, these agents enhanced the rate of disappearance of enzyme activity by greater than 12-fold, indicating a predominant effect on accelerating the rate of enzyme inactivation and/or degradation. These studies demonstrate that iodothyronines and other iodinated compounds have complex regulatory effects on 5'DI that entail alterations in the rates of both enzyme activation and inactivation. The previously accepted concept that rT3 and IOP impair thyroxine (T4) to T3 conversion in vivo by acting as competitive inhibitors is an oversimplification. Rather, the clinically beneficial effects of administering these agents to patients with hyperthyroidism may result primarily from the rapid and prolonged inactivation of 5'DI which occurs in the thyroid gland and peripheral tissues. 相似文献
32.
P. E. Wallemacq Raymond Reding Etienne M. Sokal Jean Ville de Goyet Stéphane Clement de Clety Véronique Van Leeuw Marc De Backer Jean-Bernard Otte 《Transplant international》1997,10(6):466-470
Pediatric liver transplant recipients constitute a population characterized by a particularly unpredictable and poor bioavailability
of cyclosporin (CyA). Even though several adult studies show that the new oral formulation of CyA, Neoral (NEO), produces
better bioavailability and blood level predictability, few data describe its pharmacokinetics in children. We performed a
complete analysis of the pharmacokinetics of NEO in ten small children after primary liver transplantation. Three pharmacokinetic
profiles were set up with data obtained from tests taken during i. v. administration of CyA, after the first oral NEO dose,
and after the last NEO dose before discharge from the hospital. The mean half-lives obtained were 8.1, 7.7, and 6.9 h, respectively,
and the bioavailabilities were 22 % and 21 % for the first and last NEO doses. A large interpatient variability was observed.
This was due, in part, to episodes of diarrhea that interfered with the pharmacokinetic evaluation and, in part, to the variability
of post-transplant hepatic function. There was a good correlation between CyA trough levels and their related AUCs for both
NEO profiles (r = 0.93 and r = 0.74, respectively). We conclude that, even though the pediatric OLT population remains more unpredictable than that of
adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability.
Received: 29 November 1996 Received after revision: 10 April 1997 Accepted: 15 May 1997 相似文献
33.
表小檗碱对α受体的作用 总被引:2,自引:0,他引:2
表小檗碱(epiberberine,EB)是从湖北产黄连(Coptis chinensis Franch)中提取的一种生物碱,属苯喹嗪类原小檗碱,对其药理作用的研究资料甚少,未见其对α肾上腺素体作用的报道。资料表明,许多原小檗碱类化合物有α受体阻滞作用,为从该类化合物中选择 相似文献
34.
H. Schooltink St. Rose-John 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2003,46(3):188-196
Cytokines are extracellular mediators which co-ordinate the immune system and which are essential for several differentiation processes e.g.hematopoiesis.Cytokines bind to specific receptors on the surface of target cells thereby initiating an intracellular signalling cascade leading to cytokine- and cell-specific reactions.The cytokine network is characterised by diverse regulation mechanisms and by the close interaction of different cytokine systems.Interaction and regulation takes place at the level of cytokines, its receptors and at the level of intracellular signal transduction molecules.The resulting network allows the co-ordinated response of different cell types and tissues to environmental changes.A detailed knowledge of this “language of the immunsystem” may reveal many new therapeutical strategies for the treatment of inflammation, autoimmune disease or neoplasia. 相似文献
35.
36.
Decreased blood perfusion in canine tibial diaphysis after filling with acrylic bone cement compared with inert bone wax 总被引:1,自引:0,他引:1
Sixteen dogs had one tibia filled with acrylic PMMA bone cement and the opposite, control tibia filled with inert bone wax. After 1, 4, and 12 weeks, the blood perfusion in diaphyses was measured with Sc-46 labeled microspheres. The blood flow rates increased from 1 to 4 weeks and dropped to about the 1-week level after 12 weeks on both sides, with the acrylic side lower than the control side. On both sides, Disulphine Blue staining of the bones showed severe endosteal avascularity after 1 and 4 weeks and massive periosteal apposition after 4 and 12 weeks. The initial increase in blood flow is considered due to periosteal apposition, and the differences in blood flow rates are attributed to avascularity caused by the polymerization heat and toxicity of the acrylic cement. 相似文献
37.
Ohne Zusammenfassung 相似文献
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40.
Dr. S. Søresen H. J. Kirkeby H. Stødkilde-Jørgensen J. C. Djurhuus 《Neurourology and urodynamics》1986,5(1):5-16
The pressure variations at the maximal urethral closure pressure (MUCP) were continuously recorded in healthy female volunteers by means of a two-point microtip transducer catheter for one hour. Before the investigation a normal voiding was assured objectively and bladder instability was excluded. All women showed pressure variations both at the MUCP and more distally. The pressure variations, from 3 to 66 cm H2O, showed rhythmicity and three frequency ranges could be identified. Slow pressure waves with a frequency of one in eight to 19 minutes were observed. Relatively fast-pressure waves were observed (one every one to four minutes) and relatively fast-frequency pressure waves were observed (rate: one to eight per minute). The pressure variations of the urethra seem to be an aspect of normal urethral physiology possibly contributing to continence and urinary tract infection prevention. 相似文献