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991.
Large test areas of 36 000 to 38 000 μm2 of scctioned cytoplasm/animal and organ were morphometrically evaluated for autophagic vacuoles (AVs) in heart muscle and in liver parenchymal cells. Rats were kept in a nutritional steady state by feeding a timely, i.e. shortly before the onset of darkness, single daily meal (10 g of a standard diet). Circadian variations in volume fraction as well as in numerical density of AVs were found. The values reached a maximum in the late light period, whereas minimal values were obtained in the early dark period. The variations were synchronous in heart muscle and in liver. The average cytoplasmic volume fraction of AVs in heart muscle was 0.79 × 10?4, that is less than half the value found in liver 1.74 × 10?4. The differences were less pronounced in the segregated fraction of mitochondria which amounted to 1.68 × 10?4 in heart muscle and 2.85 × 10?4 in the liver. These data suggest that in heart muscle cytoplasmic components are degraded by cellular autophagy to a similar, perhaps some lower rate than in liver. The absence of myofibrils in the AVs does not exclude a possible lysosomal degradation of myofibrillar proteins. 相似文献
992.
Aims/hypothesis Troglitazone was approved for treatment of type 2 diabetes mellitus, but by 2000 it had been removed from all world markets
due to severe drug-induced liver injury. Even today, we still do not know how many patients sustained a long-term liver injury.
No system is in place to acquire that knowledge. Regarding toxicity mechanisms, controversy persists as to which ones are
class effects of thiazolidinediones (TZDs) and which are unique to troglitazone. This study aims to provide long-term outcome
data and new insights on mechanisms of troglitazone-induced liver injury.
Methods This case series reports the liver injuries sustained by eleven type 2 diabetic patients treated with troglitazone between
1997 and 2000. Exhaustive review of medical records was performed for all patients. Long-term outcomes were available for
all the non-fatal cases. A comprehensive literature review was also performed.
Results Long-term liver injury progressing to cirrhosis was identified in seven patients. All eleven cases had liver injury patterns
consistent with troglitazone toxicity. Analysis of these cases and of the experimental troglitazone toxicity data points to
mitochondrial toxicity as a central factor. The general clinical patterns of mitochondrial hepatotoxic events are reviewed,
as are the implications for other members of the TZD family.
Conclusions/interpretation This analysis enables the liver injury induced by troglitazone to be better understood. In future cases of delayed drug-induced
liver injury that progresses after discontinuation, the possibility of mitochondrial toxicity should be considered. When appropriate,
this can then be evaluated experimentally. Such proactive investigation may anticipate clinical risk before a large-scale
therapeutic misadventure occurs. Drug-induced liver injury due to mitochondrial hepatotoxins may be less unpredictable than
has previously been surmised.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users. 相似文献
993.
M. Ashraf 《Journal of molecular and cellular cardiology》1978,10(6):535-543
Mitochondrial membranes of ischemic myocardium were studied with freeze-fracture electron microscopy. Four fracture faces, two each from inner and outer membranes, were exposed. The protoplasmic leaflet or P face contained more intramembranous (IM) particles per μm2 than the exoplasmic or E face of the same membrane. Mitochondria became swollen after coronary artery occlusion. The density of IM particles was more reduced on the outer membrane than on the inner membrane of mitochondria examined from myocardium ischemic for 45 min. Aggregation of IM particles was prominent in the tissue reperfused after 45 min of ischemia. Upon progression of ischemia the density of IM particles on both outer and inner membranes was reduced approximately by 50% in mitochondria from myocardium rendered ischemic for 2 and 24 h. More areas of the lipid bilayer which lacked IM particles were exposed in mitochondria examined from myocardium ischemic for 24 h and showed several successive undelineated fracture planes. These findings suggest that myocardial ischemia induces alterations in the lipid fluidity and the distribution pattern of IM particles of the mitochondrial membranes. 相似文献
994.
大鼠海马神经元及其线粒体增龄性改变的形态计量分析 总被引:15,自引:0,他引:15
目的探讨大鼠海马神经元及其线粒体形态结构增龄性改变的程度及性质。方法应用组织化学及电镜技术,通过计算机图像分析系统对海马神经元及其线粒体结构进行形态计量分析。结果海马CA1和CA3区神经元随增龄出现细胞皱缩,CA3区神经元数密度在老年组较青年组显著减少(P<0.05),CA1区神经元数密度各月龄组之间差异无显著性(P>0.05)。CA3区神经元胞体内线粒体体密度、数密度、比表面及嵴膜密度随增龄而减少,线粒体平均体积及平均截面积随增龄而增大。结论海马神经元及其线粒体形态结构随增龄发生显著性改变,这些形态结构的改变可能是大鼠海马老化的指征。 相似文献
995.
996.
Isolated potassium-arrested rat hearts were submitted to anoxic perfusions (30 or 100 min) at 37°C. After the period of anoxia, oxygen was re-introduced for 5 or 20 min. The ultrastructure of ventricular myocardium was studied: (1) in control experiments after 20 min stabilization period (standard perfusate, normal potassium concentration, with glucose); (2) after 35 or 105 min anoxia following the stabilization period; (3) after 5 min reoxygenation following 30 or 100 min anoxia; and (4) after 20 min reoxygenation following 100 min anoxia. During both anoxia and reoxygenation the perfusion fluid contained a high potassium concentration (17 mm) and no glucose of other substrate. After 35 min of anoxic perfusion, or 30 min of anoxic perfusion and reoxygenation for 5 min, very slight ultrastructural modifications were observed. On the other hand, marked ultrastructural modifications in myofibrils and sarcoplasmic reticulum were encountered after 105 min anoxia. But most striking morphologic changes concerning the mitochondria were observed after 5 min of reoxygenation following 100 min of anoxia. However, after 20 min reoxygenation, these mitochondrial alterations were less marked. Our results indicate that in potassium-arrested rat hearts perfused without substrate, ultrastructural alterations appeared which were dependent on the duration of the anoxic period and were greatly enhanced by reoxygenation. It is concluded that enzyme release occurring in such experimental conditions may be related to these ultrastructural alterations. 相似文献
997.
Arturo Cabarrou Irma Doria Ruben Laguens Néstor Auciello Héctor Ponce de León Héctor Caíno Norberto Cédola 《Acta diabetologica》1973,10(6):1236-1268
Resumen Diabéticos insulino dependientes, insulino independientes y controles fueron sometidos a biopsias hepáticas. El material fué
examinado con microscopia óptica y electrónica y se estudió simultáneamente en todos los casos la concentración de piruvatoquinasa
(PK). Los hallazgos a nivel citoquímico y estructural presentes en todos los diabéticos examinados consistieron en: sobrecarga
glucogénica citoplasmática y nuclear, presencia de fosfatasa alcalina en la membrana nuclear, alteraciones mitocondriales,
hipertrofia del citoplasma de las células de Kupffer con sobrecarga lipídica del mismo, disminución de las vellosidades hepatocíticas
en el espacio de Disse, presencia de invaginaciones profundas en la membrana plasmática del hepatocito y la aparición de una
membrana basal discontinua en el espacio subsinusoidal. Diabéticos insulino dependientes no presentaron valores detectables
de PK en el material obtenido por biopsia, exhibiendo en el mismo momento el mayor grado de sobrecarga glucogénica citoplasmática
y nuclear en comparación con los diabéticos insulino independientes y los controles.
Summary Liver biopsies were carried out in insulin-dependent and insulin-independent diabetics, and in controls. Biopsy material was examined under the light and electronic microscopes, and pyruvate kinase (PK) concentration was assayed simultaneously in all subjects. Cytochemical and ultrastructural changes found in all diabetics consisted in: glycogen overloading of liver cell cytoplasm and nuclei, alkaline phosphatase activity in the nuclear membrane, mitochondrial changes, hypertrophy of Kupffer cell cytoplasm with excess lipid, reduction of liver cell microvilli in Disse’s spaces, deep invaginations in liver cell plasma membranes and appearance of a discontinuous basement membrane in the subsinusoidal space. In insulin-dependent diabetics PK activity was completely lacking in the biopsy specimens, and at the same time the glycogen overloading of cytoplasm and nucleus was more marked than in non insulin-dependent diabetics and controls.
Traduzione a cura della Redazione. 相似文献
998.
R.W. Lentz C.E. Harrison J.D. Dewey D.A. Barnhorst G.K. Danielson J.R. Pluth 《Journal of molecular and cellular cardiology》1978,10(1):3-30
The function of the cardiac sarcoplasmic reticulum (SR) and mitochondria was evaluated in left ventricular papillary muscle obtained from 47 patients with non-ischemic mitral valve disease and chronic heart failure (group I) and in right ventricular crista supraventricularis muscle obtained from 29 patients with congenital subvalvular pulmonic obstruction and right ventricular hypertrophy (group II). Heart muscle was removed approximately 15 min after establishment of cardiopulmonary bypass with hypothermia and about 4 min after first aortic cross-clamping. Cat cardiac tissues were used as a technical control. The SR and mitochondria were isolated by ultracentrifugation. 45Ca uptake (5 mm sodium oxalate) and binding were quantitated by Swinny Millipore filtration. Oxidative indices were defined polarographically by use of a vibrating platinum electrode. Compared with that of the non-failing patients (group II), the SR of the failing patients (group I) showed a significant depression of Ca uptake and binding at various ATP concentrations in both the absence and the presence of Ca-stabilizing EGTA. Calcium concentration necessary for half-maximal binding (KM) to SR approximated 1 × 10?7m in each group. There was no significant difference in the Ca-stimulated SR ATPase activity of groups I and II. ADP:O ratios and NADH-linked state 4 respiration were the same in both groups. NADH- and succinate-linked respiratory control and state 3 oxygen consumption rates were significantly lower in the failing group. The addition of ruthenium red, a specific inhibitor of mitochondrial Ca transport, led to a significant reduction of NADH- and succinate-linked state 4 respiration in group I, whereas no significant effect was elicited in group II. State 3 respiration rates were not depressed by ruthenium red. In the failing human papillary muscle, a significant reduction in Ca transfer across the SR membranes is, thus, demonstrated; it seems to be accompanied by a significant increase in Ca recycling across the mitochondrial membranes. No direct correlation among biochemical alterations, hemodynamic parameters, and duration of clinical cardiac failure was found. 相似文献
999.
1000.
HBV慢性感染是诱发肝细胞癌(HCC)的首要因素之一,在HBV DNA的开放读码区S、C、P、X中,HBx基因及其所编码蛋白与HCC的关系最为密切[1],但它在转录活化中的具体机制和对病毒生命周期的影响的确切机制仍未明了,有待更深入的研究.而Raf-1作为原癌基因,对肿瘤的形成和发展起着重要作用,在促进肿瘤细胞增殖的同时,作为抗凋亡基因,阻止细胞凋亡的发生[2].本研究试图探讨HBx诱导Raf-1线粒体转位的现象及其机制. 相似文献