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1.
Summary The time course of the reversal of toxic and nontoxic effects of digoxin by digoxin-specific antibody fragments (Fab) was measured in isolated human ventricular myocardium. A concentration of 2×10–6 mol/l digoxin was used to produce positive inotropy followed by mechanical signs of toxicity. After addition of a 1.5-fold higher molar concentration of digoxin-specific Fab, signs of toxicity disappeared within 30 min and digoxin-induced force of contraction decayed with a monoexponential time course with a half-life of 52 min. This rate of decay was almost identical to that observed for the dissociation of the digoxin-(Na++K+)-ATPase complex in human heart cell membranes. It is concluded that (a) digoxin-specific Fab are capable of completely removing digoxin from its binding sites, (b) the maximal rate of removal of digitalis glycosides from the (Na++K+)-ATPase is limited by the dissociation rate constant, and (c) there is a close correlation between the degree of binding of digitalis glycosides to the (Na++K+)-ATPase and the increase in force of contraction.Abbreviation Fab
Fragment antibody binding (digitalis antidote) 相似文献
2.
Summary Dehydro-digitoxosides are metabolites of digitalis glycosides. In order to study their possible biological activity their affinity to (Na++K+)-activated ATPase was determined and compared with unchanged glycosides. Based on the dissociation constants of glycoside-enzyme-complexes, the affinity of the dehydro-digitoxosides ranged in the same order of magnitude as that of the native glycosides. Comparing mono-, bis-, and tris-digitoxosides of digitoxigenin (dt-1, dt-2, dt-3) and of digoxin (dg-1, dg-2, dg-3) with the corresponding dehydrodigitoxosides (3-dehydro-dt-1, 9-dehydro-dt-2, 15-dehydro-dt-3, 3-dehydro-dg-1 and 9-dehydro-dg-2, respectively) the dehydro-digitoxosides had lower affinities to the enzyme. The highest dissociation constants (K
D)were found for 3-dehydro-dt-1 and 3-dehydro-dg-1. The half maximal inhibition of (Na++K+)-ATPase activity (I50) corresponded to affinity measurements in all but two cases: dehydro-dt-3 and dehydro-dt-2 showed very low I50 values. 相似文献
3.
4.
Bahadir Kirilmaz Serkan Saygi Hasan Gungor Ugur Onse Turk Emin Alioglu Serdar Akyuz Fatih Asgun Istemihan Tengiz Ertugrul Ercan 《老年心脏病学杂志》2012,9(3):237-242
Objectives Although development of new treatment modalities limited digoxin usage, digoxin intoxication is still an important issue which could be easily overlooked. In this report we analyzed a case series definitively diagnosed as digoxin intoxication in the modern era. Methods We analyzed 71 patients hospitalized with digoxin intoxication confirmed by history, complaints, clinical and electrocardiograph (ECG) findings, and serum digoxin levels > 2.0 ng/mL, during a five year period. The demographic and clinical data, indications for digoxin use, digoxin dosage, concurrent medications, laboratory data, hospital monitoring, and ECG findings were obtained from all patients. Results Thirty-eight of 71 patients (53.5%) had symptoms of heart failure during admission or later. Sixty-four percent of patients were older than 75 years. The percentage of females was 67%. Atrial fibrillation, hypertension and gastrointestinal complaints were more frequent in the females (64% in females, 30% in males, P = 0.007; 81% in female, 52% in males, P = 0.01; 50% in female, 17.3% in males, P = 0.008, respectively). The mortality rate during the hospital course was 7%. Conclusion This report demonstrated the reduced mortality rates in patients with digoxin intoxication over the study period. Gastrointestinal complaints are the most common symptoms in this population. 相似文献
5.
Grzegorz Grześk Wioleta Stolarek Michał Kasprzak Marek Krzyżanowski Katarzyna Szadujkis-Szadurska Michał Wiciński Elżbieta Grześk 《Pharmacological reports : PR》2018,70(1):184-189
Background
Digoxin is the oldest drug used in the pharmacotherapy of heart failure (HF). However, digoxin remains an important therapeutic option for patients with persistent symptoms of HF occurring despite the implementation of standard pharmacotherapy. Digoxin concentration serum (SCD) should equal 1–2 ng/ml. The aim of our study was to measure of SCD among the hospitalized patients as well as to determine the selected factors influencing the concentration of the digoxin in the blood.Methods
The presented research was based on a retrospective analysis including 2149 patients treated with digoxin and hospitalized between 1980 and 2000. Was used for the determination of SCD automatic analyzer TDX ABBOTT GmbH – fluorescence polarization immunoassay (FPIA), with therapeutic range for digoxin of 0.8–2.0 ng/ml.Results
Average SCD result in the study population was located within the therapeutic range and amounted 1.06 ng/ml (55.7% of patients). Statistically significant differences in digoxin level were observed depending on the way of medicine administration (p = 0.000001) and the daily amount (p = 0.001). Moreover, statistically significant differences in digoxin level were observed depending on sex (p = 0.00002).Conclusions
An elevated level of digoxin was observed in the case of patients who received the medication both orally and intravenously, together with an increase in the daily amount of digoxin doses. It was confirmed that an elevated digoxin level occurs in the course of treatment in the case of women. 相似文献6.
Andre Gervais Ulrich Busch Jeanie M. Wood Arnold Schwartz 《Journal of molecular and cellular cardiology》1978,10(11):1003-1015
The effects of toxic doses of ouabain on two parameters of mitochondrial activity, oxidative phosphorylation and calcium uptake were examined. Ouabain was injected intraperitoneally into guinea-pigs until signs of severe intoxication appeared. State 3 oxygen consumption (QO2, State 3, in natom oxygen/mg/min) of isolated heart mitochondria was 314 ± 16 and 281 ± 16 (glutamate-malate) for treated and control group, respectively; 225 ± 21 and 207 ± 23 (pyruvate-malate), and 251 ± 12 and 230 ± 13 (succinate), respectively. The rate of calcium uptake was 411 nmol Ca2+/min/mg for treated and 329.6 nmol Ca2+/min/mg for control. The rate of calcium release was the same in control and treated groups.The data suggest that increases of respiration and calcium uptake in vitro, if they reflect similar increases in vivo, may contribute to digitalis intoxication by intracellular redistribution of calcium. 相似文献
7.
目的 比较心先安与洋地黄治疗慢性心力衰竭的疗效。方法 将120例心衰患者随机分成心先安组(n=60)和洋地黄组(n=60)。心先安组给予心先安120mg~150mg加入5%葡萄糖盐水250ml中静脉滴注,连续10日~14日;洋地黄组给予地高辛0.125mg或0.25mg口服,每日1次。结果 心力衰竭临床症状改善的有效率,心先安组为82%;洋地黄组为84%,两组间无显著差异(P〉0.05)。结论 心先安是一种疗效可靠,无明显毒副作用的强心、扩血管药物。 相似文献
8.
儿童体外循环内源性类洋地黄物质变化 总被引:3,自引:0,他引:3
目的 探讨内源性类洋地黄物质与儿童心功能之间的关系及其在体外循环期间变化的临床意义。方法 80例先天性心脏病患儿根据心功能分级分为4组,按先天性心脏病分类分为2组,于术前,主动脉阻断后,转流30min,心脏复苏后和术后24h测定血浆EDLS浓度。结果 (1)儿童血浆EDLS浓度在心功能代偿期与正常对照组无显著性差异,而心功能不全各级分别显著高于正常组,并随心功能不全程度加重而增加;(2)体外循环期间以循环阻断后EDLS浓度最低,随着心脏复苏EDLS浓度逐渐升高,至术后24h EDLS浓度恢复至术前水平;(3)青紫型先天性心脏病与非青紫型先天性心脏病比EDLS血清浓度有显著性差异,而转流期间变化不大。结论 (1)EDLS血浆浓度与心功能不全的严重程度呈密切相关,成为维持心脏功能代偿的因素之一;(2)EDLS随容量负荷增加而增加;(3)儿童心脏病术后适当应用洋地黄制剂是安全的。 相似文献
9.
A method described by Bieltvedt & Briseid (1966) and Bieltvedt (1967) for the determination of the inhibition by cardiac glycosides of the isolated, histamine-stimulated guinea pig ileum was modified to estimate the inhibition of the acetylcholine-stimulated rat jejunum. The glycoside concentrations causing 50 % inhibition of submaximal, isotonic contractions were determined, and the procedure was based on 20-minute contact periods between the muscle preparations and the cardioactive substances, and then 22-minute equilibration periods with chemical stimulation. The degree of inhibition was found to depend on the potassium content of the Tyrode solutions used. In a low potassium Tyrode solution (1.8 mM) the inhibition of the rat intestine by cardiac glycosides was found to be of the same order of magnitude as the inhibition of the guinea pig intestine. When the potassium chloride concentration was increased to 2.7 mM, the well known species difference was observed, the concentration of cardiac glycoside required for inhibition of the rat intestine being about 30 times higher than that required for inhibition of the guinea pig intestine. The range of potency of the different cardiac glycosides and aglycones which were tested in the low potassium. Tyrode solution, was the same for the two species. Presupposing an inhibition of Na+, K+-activated transport ATPases as the basic mechanism for the inhibition by cardiac glycosides of the isolated intestine preparations, a theory of qualitative differences between the transport enzymes in the two species is advanced. In the rat intestine the presence is suggested of one ATPase which is rather resistant to inhibition by cardiac glycosides, but sensitive to a reduction in potassium concentration, in addition to a glycoside-susceptible ATPase also present in the guinea pig intestine. 相似文献
10.
目的:观察慢性充血性心力衰竭中心气(血)虚证和心阴不足证患者血清内源性洋地黄因子含量的变化,探讨其临床意义。方法:以放免法测定正常人与慢性充血性心动力衰竭患者中心气(血)虚组与心阴不足组内源性洋地黄因子的含量。结果:心气(血)虚患者内源性洋地黄因子含量比心阴不足型显著下降(P<0.01)。结论:内源性洋地黄因子分泌减少可能是导致中医心气(血)不足的主要原因之一,而心阴不足证患者内源性洋地黄因子含量比心气(血)虚证患者降低程度小,提示在中西医结合治疗中对前类患者使用洋地黄药物效果可能更好,而对后类患者应谨慎使用洋地黄类药物。 相似文献