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MARC A. VOS Ph .D. ANTON P.M. GORGELS M.D. GYORGYI C. LIPCSEI M.D. S.H. MARIEKE de GROOT M.S. JET D.M. LEUNISSEN HEIN J.J. WELLENS M.D. 《Journal of cardiovascular electrophysiology》1994,5(9):731-742
Mechanism-Specific Action of Levcromakalim. Introduction: The hypothesis that levcromakalim. a potassium channel (IK-ATP.) activator with antihypertensive properties, has a mechanism-specific antiarrhythmic action against repolarization-dependent ventricular tachycardias (VTs) was tested in dogs. Methods and Results: A low dose of leveromakalim (0.01 mg/kg) was selected, which decreased blood pressure by 25% but had almost no electrophysiologic effect on AV nodal or ventricular conduction or effective refractory period. In dogs with chronic AV block, the antiarrhythmic action of this dose of levcromakalim was evaluated in three models of abnormal impulse formation: (I) dsotalol (2 mg/kg) induced torsades de pointes VT, initiated by early afterdepolarizations (EADs). (2) sustained ouabain-induced VTs, which are dependent on delayed after depolarizations (DADs), and (3) VT occurring 24 hours after left anterior descending coronary artery occlusion, which are likely based on abnormal automaticity. Levcromakalim abolished d-sotalol induced U waves, ventricular ectopic beats, and self-terminating bouts of torsades de pointes. Induction of torsades de pointes by pacing was also completely prevented. The cycle length of the idioventricular rhythm, which was lengthened after d-sotalol from 1490 ± 515 to 1700 ± 610 msec (P < 0.05), remained similar after levcromakalim (1655 ± 580 msec). The QT(U) duration, which was increased after d-sotalol from 410 ± 55 to 550 ± 40 msec (P < 0.05), normalized to 405 ± 70 msec (P < 0.05). Lcvcromakulim did not suppress but rather enhanced ouabain-induced VT by decreasing the cycle length slightly from 315 ± 35 to 290 ± 35 msec (P < 0.05). Pretreatment with a beta Mocker prevented this acceleration in rate. Finally, levcromakalim had no effect on VT 24 hours after infarction. Conclusion: A low dose of levcromakalim has specific antiarrhythmic properties against repolarization-dependent arrhythmias, but it does not affect VTs based on other mechanisms of abnormal impulse formation. 相似文献
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Growth into a professional role requires absorption of knowledge, the learning of skills and the adoption of behavioural patterns and values which are part of a particular profession. In sociological literature this is described as the socialization/professionalization process. In this article the research literature which describes the process is reviewed. However, apart from the many positive aspects of adjusting and conforming, there are also more negative developments in the learning behaviour and attitudes of the future doctor. The Department of Medical Psychology in Amsterdam has structured its teaching programme--in part--to overcome or to decrease such tendencies. This article deals with those parts of the course which attempt to influence medical students' interviewing and interpersonal skills. Research into the effects of this teaching points to a marginal influence in both areas. The author looks for explanations for this, in the light of the research literature. In conclusion, the direction is indicated which could further increase the influence of the medical psychology course on future doctors. 相似文献
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SINISA RADULOVIC REN-ZHI CAI PETER SERFOZO KATE GROOT TOMMIE W. REDDING JACEK PINSKI ANDREW V. SCHALLY 《Chemical biology & drug design》1991,38(6):593-600
In an attempt to produce more powerful (effective) bombesin/GRP receptor antagonists, the d forms of Trp or Trp analog (Tpi) were introduced at position 6 in two pseudononapeptides, Leu13Ψ (CH2NH)Leu14-bombesin(6-14) and Leu13Ψ(CH2NH)Phe14 -bombesin (6-14). These antagonists were tested for their ability to inhibit basal and gastrin releasing peptide (GRP) (14-27)-induced amylase release from rat pancreatic acini in a superfusion assay. They were also assessed for the inhibition of 125I-Tyr4 -bombesin binding to Swiss 3T3 and small cell lung carcinoma cell line H-345 and the mitogenic response of Swiss 3T3 cells induced by GRP(14-27). The peptides, when given alone, did not stimulate amylase secretion, but were able to inhibit gastrin releasing peptide (14-27)-induced amylase release. All of the antagonists showed strong binding affinities for Swiss 3T3 and H-345 cells and suppressed the GRP(14-27)-induced increase of [3H]thymidine incorporation into DNA of Swiss 3T3 cells at nanomolar concentrations. Antagonist d -Tpi6,Leu13Ψ (CH2NH)Leu14-bombesin (6-14)(RC-3095) was slightly more potent in these assays than d -Trp6,Leu13Ψ (CH2NH)Leu14-bombesin (6-14)(RC-3125). Nevertheless, d -Trp6 Leu13Ψ (CH2NH)Phe14-bombesin (6-14) showed the highest binding affinity for Swiss 3T3 and H345 cells and it was the most potent inhibitor of GRP(14-27)-induced amylase secretion. This antagonist RC-3420 was particularly effective in inhibiting the growth of Swiss 3T3 cells, exhibiting an IC50 value less than 1 nm . Our work indicated that the substitution of d -Trp and d -Tpi at position 6 of the pseudononapeptide bombesin analogs (Ψ13-14), in which the Met14 residue is replaced by Leu or Phe, results in potent bombesin/GRP antagonists with improved in vivo activity. 相似文献
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Endothelial cell dysfunction in homocystinuria 总被引:10,自引:0,他引:10
PHILIP G. DE GROOT CHARLES WILLEMS GODFRIED H. J. BOERS MERVIN D. GONSALVES WILLEM G. VAN AKEN JAN A. VAN MOURIK 《European journal of clinical investigation》1983,13(5):405-410
Abstract. This report describes the isolation and culture of venous endothelial cells from the umbilical cord of an obligate heterozygote for homocystinuria. The effect of different sulphur-containing amino acids on the viability and function of these cells was studied and compared with cultured normal endothelial cells. When endothelial cells were cultured in the presence of methionine (10 mmol/l) or homocystine (10 mmol/l), differences occurred between the viability and function of the heterozygote and normal cells in terms of 51 Cr release and ability to prevent platelet adherence. The Cr release corrected for spontaneous release increases for the heterozygote cells after incubation for 21 h in the presence of methionine to 81.3% (control cells, range: 0–23.3%, n = 5) and in the presence of homocystine to 141% (control cells, range: 13.5–55.2%, n = 5). The total number of platelets that adhere to confluent monolayers increases for heterozygote cells cultured in the presence of methionine to 0.98 ± 107 platelets cm-2 (normal cells, range: 0.56–0.72 ± 107 platelets cm-2 ) and in the presence of homocystine to 1.41 ± 107 platelets cm-2 (normal cells, range: 0.94–1±06 ± 107 platelets cm-2 ). Both normal and control cells were sensitive to homocysteine. This study indicates for the first time what vascular endothelial cells, derived from an obligate heterozygote, are (partly) deficient in cysthathionine synthase and are more susceptible to methionine- and homocystine-mediated injury than normal endothelial cells. Consequently, in homocystinuria, due to dysfunction of the endothelial cells, toxic sulphur-containing amino acids may accumulate in these cells, causing injury of these cells. 相似文献