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991.
992.
To investigate the intrahepatic disposition of drugs subjected to the first-pass effect, propranolol (0.002 mg/kg and 5 mg/kg) was injected into the portal vein of rats. At various times the drug was measured in liver homogenate, cytosol, smooth microsomal, and Golgi fractions. The results suggest that hepatic uptake of propranolol is an extremely rapid process and essentially complete, independently of the dose. Effectively at 0.5 min, 70% and 85% of the low and high doses, respectively, were recovered in the liver homogenate. Furthermore following the 0.002-mg/kg dose, 96% of the recovered drug equivalents in the suprahepatic blood consisted of metabolites. An additional experiment demonstrated that the uptake of a 0.002-mg/kg dose of propranolol was not modified by a loading dose of 25 mg/kg. The pattern of propranolol distribution correlated with the intracellular localization of phospholipids and proteins. The amount of propranolol found in subcellular fractions relative to liver homogenate remained constant throughout the study, suggesting a rapid equilibrium. Low doses of propranolol were cleared from the hepatic cells almost completely by biotransformation. However, high doses saturated the metabolic clearance. Propranolol metabolites accumulated preferentially in the cytosol fraction. The intracellular elimination of the metabolites appeared to be a saturable process. The Golgi apparatus does not seem to be involved in the elimination of propranolol or its polar metabolites. 相似文献
993.
994.
F P Retief A du Heyns M Oosthuizen O R van Reenen 《Suid-Afrikaanse tydskrif vir geneeskunde》1976,50(7):212-216
After 14C-methyl folate (14C-MeTHF) was taken by mouth, progressive incorporation of this istope into the dialysis-resistant plasma folate fraction occurred. At 6 hours 68,9% of the total plasma radioactive folate was dialysis-resistant. We have previously shown that 14C-folic acid (14C-PGA) taken by mouth is not similarly bound at 6 hours. Chromatography of plasma on DEA A50 after 14C-PGA absorption, showed that PGA in plasma (peak 1) was gradually converted to MeTHF (peak 2) and the absence of bound radiofolate 6 hours after 14C-PGA ingestion probably reflects this conversion phase. No radiofolate appeared in red cells up to 11 days after isotope ingestion. Initial divergence between plasma biofolate and radiofolate indicated that 'cold' storage folate was being displaced by abosrbed radiofolate. Urinary radiofolate resolved into 3 fractions (peaks 2, 3 and4) on DEAE A50 chromatography. One of these (peak 2) corresponded to MeTHF, but PGA (peak 1) was absent. Plasma showed peaks 1, 2 and 3, but at 3 hours no equivalent of urinary peak 4 was evident. Further studies are indicated to characterise fractions 3 and 4. 相似文献
995.
F. P. Retief A. du P. Heyns Mariëtha Oosthuizen O. R. van Reenen C. J. Badenhorst 《British journal of haematology》1976,32(1):113-122
It is useful to differentiate between saturated folate binders in serum (carrying endogenous folate) and unsaturated binders (investigated in the present study). These two groups of binders need not necessarily be chemically identical and the unsaturated binder may even be an in vitro artifact, especially when measured with non-physiological folates. Macromolecular binding of radio-active N-5-methyl tetrahydrofolic acid (CH3H4PteGlu) and/or folic acid (PteGlu) by human serum and urine was assessed by means of exhaustive saline dialysis, haemoglobin-coated charcoal adsorption, column chromatography with DEAE-Sephadex A-50, and sucrose gradient analysis. Binding was found to be minimal or absent. Charcoal adsorption showed a mean serum binding capacity of 0 mug/1. for PteGlu and 0.58 mug/1. for CH3H4PteGlu. In pregnancy the mean serum values were 0.23 mug/1. for PteGlu, 0.66 mjg/1. for CH3H4PteGlu, and with folate deficiency 0.30 mug/1. for PteGlu, 0.49 mug/1. for CH3H4PteGlu. Mean urinary folate binding was minimal (less than 0.5 mug/1.), and red cell haemolysate similarly revealed very low binding on exhaustive dialysis. Column chromatography showed that tracer doses of [14C]PteGlu added to serum migrated distally to the protein zone; [14C]CH3H4PteGlu similarly showed no evidence of protein binding. On a sucrose gradient [14C]PteGlu also separated clear of the protein zone. 相似文献
996.
997.
998.
Identification of hydrallazine and hydrallazine hydrazone metabolites in human body fluids and quantitative in vitro comparisons of their smooth muscle relaxant activity 下载免费PDF全文
K D Haegele A J McLean P du Souich K Barron J Laquer J L McNay O Carrier 《British journal of clinical pharmacology》1978,5(6):489-494
1 Serum and urine from hypertensive subjects on chronic oral hydrallazine therapy were studied using gas chromatographic/mass spectrometry techniques. 2 Metabolites resulting from acetylation, hydrolysis and conjugation reactions were detected. The acetone, pyruvate and alpha-ketoglutarate hydrazone were identified. 3 The activity of the pyruvate and alpha-ketoglutarate hydrazones were compared with that of hydrallazine using isolated rabbit aortic strips. 4 Both hydrazones were active under in vitro conditions, producing smooth muscle relaxant effects equal to those of hydrallazine. 5 It is concluded that hydrazone metabolites will contribute to the hypotensive effects of hydrallazine therapy in proportion to their relative abundance, persistence in vascular tissues and intrinsic activity. 相似文献
999.
A comparison of certain rat strains with respect to susceptibility to nephrocalcinosis 总被引:1,自引:0,他引:1
D B du Bruyn 《Suid-Afrikaanse tydskrif vir geneeskunde》1970,44(49):1417-1418
1000.
J M Hugo M J Ungerer F R Erasmus P W du Toit F O Muller D J van Velden 《Suid-Afrikaanse tydskrif vir geneeskunde》1978,53(20):807-810
A case of malignant hyperthermia in a Black boy is presented. He developed this condition during repair of a cleft palate, with halothane as the triggering agent. The importance of the high incidence of malignant hyperthermia in patients with certain musculoskeletal abnormalities is stressed. Despite a cool and well air-conditioned theatre, the patient's temperature was 41 degree C when the condition was suspected. At that stage general muscle rigidity was present. The patient was successfully treated with procainamide, sodium bicarbonate and hydrocortisone; surface cooling (with ice packs) was instituted and the stomach was washed out with ice-cold Ringer's solution. Over a period of 14 days serum creatine phosphokinase values decreased from 630 IU (on the day of the incident) to 12 IU. A muscle biopsy showed variation in muscle fibre size. Electron microscopical studies showed myofibrillar disruption and folding of the basement membrane. A modified version of Denborough's technique was used for the in vitro exposure of muscle strips to halothane and suxamethonium. Isometric contraction was measured and recorded. A severe contraction followed the exposure of muscle strips to halothane, which confirmed the diagnosis. 相似文献