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101.
Foa R; Pelicci PG; Migone N; Lauria F; Pizzolo G; Flug F; Knowles DM d; Dalla- Favera R 《Blood》1986,67(1):247-250
We investigated the rearrangement patterns of the gene coding for the beta chain of the T cell receptor (T beta) in 11 patients with T-cell derived chronic lymphoproliferative disorders, including T-cell prolymphocytic leukemia (T-PLL) and T-cell chronic lymphocytic leukemia (T-CLL). We found that all five cases of T-PLL, and five of six cases of T-CLL, displayed T beta-gene rearrangements, clearly establishing their monoclonal nature. Clonality could not be determined in one case of T-CLL where the T beta gene was found unrearranged. Our results demonstrate that the majority of cases of both clinically aggressive T- PLL and clinically indolent T-CLL are monoclonal. These results suggest that the analysis of T beta gene rearrangements represents a valid tool for the differential diagnosis and clinical monitoring of T-cell derived chronic lymphoproliferative diseases. 相似文献
102.
Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis 总被引:20,自引:0,他引:20
To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant- induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine- xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis. 相似文献
103.
Dr. D. P. Girvan MCISc FRCS J. Hansky MB FRACP J. Spencer MB FRCS J. H. Baron DM FRCP 《Digestive diseases and sciences》1974,19(11):977-986
The intravenous infusion of insulin 0.04 U/kg-hr for 2-1/2 hours was performed in 26 patients with chronic duodenal ulcer. In 15 patients this infusion test was compared with the standard test of a single intravenous injection of insulin 0.2 U/kg. The mean lowest blood glucose level in the infusion group (25.1 mg/100 ml) was significantly higher than in the standard test (17.4 mg/100 ml), and the interval from injection to acid stimulation about twice as long (75versus 45 minutes). The peak acid output and mean rise in acidity were comparable in the two procedures. Serum gastrin responded reciprocally to insulin-induced hypoglycemia with a significant inverse correlation between blood glucose and gastrin. In 13 patients tested after vagotomy, there was no significant difference in the rise in acidities in the two groups, and the Hollander status was the same in all but one patient. The mean basal, peak, and absolute rise of serum gastrin in unoperated patients and patients with incomplete vagotomy were almost identical. In patients with complete vagotomy there was no significant rise in serum gastrin after insulin infusion. Unpleasant side effects as assessed by an independent observer were fewer and less severe in patients undergoing infusion tests than in the standard test. The insulin infusion test is recommended as a safer and more acceptable test than the standard insulin test since it avoids severe hypoglycemia and has milder side effects yet achieves comparable acidity and acid outputs. Measurements of serum gastrin after either insulin test provide no additional information helpful in the assessment of the completeness of vagotomy. 相似文献
104.
The effect of PGI2 and theophylline on the response of platelets subjected to shear stress 总被引:2,自引:0,他引:2
A specially designed rotational viscometer was used to investigate the effects of the antiplatelet agent PGI2 in combination with theophylline on the response of human platelets subjected to shear stress. Samples of citrated platelet-rich plasma (PRP) were exposed to shear stress in the viscometer for a period of 5 min at 23 degrees C. The levels of stress studied ranged from 50 to 300 dynes/sq cm. Pretreatment of the platelets with 0.01 microM PGI2 and 500 microM theophylline before exposure to shear stress caused a large reduction in shear-induced platelet aggregation. However, it was also observed that the PGI2-- theophylline pretreatment concomitantly caused a large increase in shear-induced platelet lysis and serotonin release at stress levels equal to or greater than 150 dynes/sq cm. This observed increase in platelet fragility may have important implications for clinical applications of PGI2. The results are discussed and compared to those obtained in prior work in which platelets were pretreated with acetylsalicylic acid or with PGE1. 相似文献
105.
Oxidants released from inflammatory cells contribute to the pathogenesis of acute inflammatory edema in many models. Chemically produced oxidants can reversibly alter the barrier properties of cultured endothelial and epithelial monolayers. This report examines the effects of nonlytic doses of H2O2 on endothelial cell lipids. H2O2 oxidized omega-6 fatty acids in the endothelial cells and initiated hydrolysis of endothelial cell phospholipids. When endothelial cells were exposed to peroxidized linoleic acid, it caused lysis of the cells at doses 1,000-fold lower than effective doses of H2O2. The phospholipid hydrolysis was directed primarily at the inositol phospholipids and consisted of both A and C type phospholipase activity. The phospholipase A hydrolysis resulted in increases in endothelial cell free fatty acids and lysophosphatidylinositol. The phospholipase C hydrolysis resulted in increases in diglycerides, phosphatidic acid, and inositol polyphosphate levels. The phospholipase C hydrolysis of phosphatidylinositol is known to activate protein kinase C in most cells. Stimulation of protein kinase C with phorbol- 12,13-dibutyrate increased albumin flux across endothelial monolayers and altered endothelial cell shape, similar to effects of oxidants. These data are consistent with the hypothesis that oxidant-initiated hydrolysis of endothelial cell inositol phospholipids contributes to oxidant-mediated reversible changes in endothelial monolayer barrier function. 相似文献
106.
Morten Wøjdemann M.D. Pernille Traberg Flemming Stadil DM.Sci Berit Sternby Ph.D. Steen Larsen DM.Sci Linda Hilsted DM.Sci Ole Olsen DM.Sci 《The American journal of gastroenterology》1998,93(2):244-248
Objective : Gastric lipase and gastric acid are secreted simultaneously. The aim of this study was to investigate whether the acid interferes with the lipase secretion. The secretion of human gastric lipase was studied during blockade of gastric acid secretion and modified sham feeding to estimate the impact of these conditions on both gastric lipase enzyme activity and immunoreactivity. Methods : Eight healthy volunteers were intubated with a nasogastric tube. We examined gastric aspirates for the amount and activity of lipase secretion during basal conditions, after blockade of acid secretion with a proton pump inhibitor (omeprazole i.v. infusion), and in response to sham feeding (chewing gum) during the blockade. Results : The amount of secreted gastric lipase was unaffected by blockade of acid secretion and increased significantly after sham feeding (169.9 ± 35.7 g/15 min to 348.1 ± 79.2 g/15 min; p < 0.01 ). Likewise, the output of enzyme activity increased after sham feeding (0.63 ± 0.09 kU/15 min to 1.52 ± 0.36 kU/15 min; p < 0.03 ). The concentration of enzyme activity remained unchanged by blockade of acid secretion, whereas the output of enzyme activity was decreased, probably because of reduced volume secretion or denaturation and conformational changes of the enzyme. Plasma concentrations of gastrin increased in response to blockade of acid secretion (basal 9.6 ± 1.4 pmol/L to 13.3 ± 2.9 pmol/L; p < 0.02 ). Conclusions : Gastric acid secretion is not a prerequisite for gastric lipase secretion. Lipase enzyme activity, though, is sensitive to anacidic conditions. 相似文献
107.
In a previous study we have shown that monoclonal antibody F1 (MoAb F1), directed against an epitope on the heavy chain of factor XII distinct from the binding site for anionic surfaces, is able to activate factor XII in plasma (Nuijens JH, et al: J Biol Chem 264; 12941, 1989). Here, we studied in detail the mechanism underlying the activation of factor XII by MoAb F1 using purified proteins. Formation of factor XIIa was assessed by measuring its amidolytic activity towards the chromogenic substrate H-D-Pro-Phe-Arg-pNA (S-2302) in the presence of soybean trypsin inhibitor and by assessing cleavage on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Upon incubation with MoAb F1 alone, factor XII was auto-activated in a time-dependent fashion, activation being maximal after 30 hours. Factor XII incubated in the absence of MoAb F1 was hardly activated by kallikrein, whereas in the presence of MoAb F1, but not in that of a control MoAb, the rate of factor XII activation by kallikrein was promoted at least 60-fold. Maximal activation of factor XII with kallikrein in the presence of MoAb F1 was reached within 1 hour. This effect of kallikrein on the cleavage of factor XII bound to MoAb F1 was specific because the fibrinolytic enzymes plasmin, urokinase, and tissue-type plasminogen activator could not substitute for kallikrein. Also, trypsin could easily activate factor XII, but in contrast to kallikrein, this activation was independent of MoAb F1. SDS-PAGE analysis showed that the appearance of amidolytic activity correlated well with cleavage of factor XII. MoAb F1-induced activation of factor XII in this purified system was not dependent on the presence of high- molecular-weight kininogen (HK), in contrast to the activation of the contact system in plasma by MoAb F1. Experiments with deletion mutants revealed that the epitopic region for MoAb F1 on factor XII is located on the kringle domain. Thus, this study shows that binding of ligands to the kringle domain, which does not contribute to the proposed binding site for negatively charged surfaces, may induce activation of factor XII. Therefore, these findings point to the existence of multiple mechanisms of activation of factor XII. 相似文献
108.
109.
John L. Reid DM Robert J. MacFadyen MD PhD Iain B. Squire MB Kennedy R. Lees MD 《The American journal of cardiology》1993,71(17):E57-E60
Angiotensin-converting enzyme (ACE) inhibitors improve survival in heart failure and delay progression to clinical heart failure in patients with left ventricular dysfunction after myocardial infarction. Increasing numbers of older patients are being considered for such treatment. However, there are reports of excessive and prolonged decreases in blood pressure (BP) after the first dose of some ACE inhibitors. We have studied the hemodynamics, pharmacokinetics, and neurohumoral responses to the first dose of oral captopril 6.25 mg, enalapril 2.5 mg, perindopril 2.0 mg, intravenous enalaprilat 1.5 mg, and perindoprilat 1.0 mg, compared with oral or intravenous placebo in 6 parallel groups of 12 elderly patients each with moderate-to-severe (New York Heart Association classes II-IV) heart failure. Oral dosing with active drugs led to different temporal responses. After captopril, there was an early short-lived decrease in BP. Enalapril led to a later long-lasting decrease, but perindopril was not different from placebo. Intravenous enalaprilat and intravenous perindoprilat each lowered BP to a similar extent. The doses of drugs used appeared to be comparable because plasma ACE inhibition was similar following perindopril or enalapril and also comparing perindoprilat and enalaprilat. These studies indicate that oral ACE inhibitors have different profiles of acute BP changes after the first dose. The explanation is not clear, but could include physicochemical differences in the interaction between prodrug ester and diacid metabolites leading to differences in tissue distribution and local enzyme inhibition. 相似文献
110.
Erectile Impotence in Chronic Alcoholics 总被引:1,自引:0,他引:1
Edward T. H. Tan BSc PhD Ralph H. Johnson DM DSc FRCP David G. Lambie BSc PhD Mithra E. Vijayasenan MB BS FRANZCP Edwin A. Whiteside MB ChB 《Alcoholism, clinical and experimental research》1984,8(3):297-301
Erectile impotence is a common complaint in alcoholics, but its mechanism is unknown. We have studied nocturnal penile erection in 13 alcoholics who complained of impotence. Seven had normal erections and their impotence was therefore psychogenic. Six were found to have diminished or absent nocturnal erections. Plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were elevated in this latter group, with the exception of one patient who had only raised FSH. They also had more evidence of neurological damage than the other seven alcoholics, and two had evidence of damage to the parasympathetic nervous system. Investigation of erection during sleep in alcoholic patients with impotence may be useful in differentiating clinically between patients with psychogenic causes and patients with organic causes of impotence. 相似文献