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1.
Noninvasive imaging of cardiac fibrosis is important for early diagnosis and intervention in chronic heart diseases. Here, we investigated whether noninvasive, contrast agent-free MRI T2-mapping can quantify myocardial fibrosis in preclinical models of aging and pressure overload. Myocardial fibrosis and remodeling were analyzed in two animal models: (i) aging (15-month-old male CF-1 mice vs. young 6- to 8-week-old mice), and (ii) pressure overload (PO; by transverse aortic constriction in 4- to 5-month-old male C57BL/6 mice vs. sham-operated for 14 days). In vivo T2-mapping was performed by acquiring data during the isovolumic and early diastolic phases, with a modified respiratory and ECG-triggered multiecho TurboRARE sequence on a 7-T MRI. Cine MRI provided cardiac morphology and function. A quantitative segmentation method was developed to analyze the in vivo T2-maps of hearts at midventricle, apex, and basal regions. The cardiac fibrosis area was analyzed ex vivo by picro sirius red (PSR) staining. Both aged and pressure-overloaded hearts developed significant myocardial contractile dysfunction, cardiac hypertrophy, and interstitial fibrosis. The aged mice had two phenotypes, fibrotic and mild-fibrotic. Notably, the aged fibrotic subgroup and the PO mice showed a marked decrease in T2 relaxation times (25.3 ± 0.6 in aged vs. 29.9 ± 0.7 ms in young mice, p = 0.002; and 24.3 ± 1.7 in PO vs. 28.7 ± 0.7 ms in shams, p = 0.05). However, no significant difference in T2 was detected between the aged mild-fibrotic subgroup and the young mice. Accordingly, an inverse correlation between myocardial fibrosis percentage (FP) and T2 relaxation time was derived (R2 = 0.98): T2 (ms) = 30.45 – 1.05 × FP. Thus, these results demonstrate a statistical agreement between T2-map–quantified fibrosis and PSR staining in two different clinically relevant animal models. In conclusion, T2-mapping MRI is a promising noninvasive contrast agent-free quantitative technique to characterize myocardial fibrosis. 相似文献
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Summary We compared thein-vitro activity of cefoperazone-sulbactam (2 : 1), other -lactams, aminoglycosides and ciprofloxacin against cefoperazone-susceptible and -resistant nosocomial gram-negative bacilli. Resistant isolates includingPseudomonas aeruginosa were susceptible to cefoperazone-sulbactam; the susceptible isolates had modestly increased susceptibility to the combination. Sulbactam, by itself, was poorly active. Among others tested, ciprofloxacin and imipenem were the most active. No inoculum effect was seen with cefoperazone-sulbactam and this drug combination had a prolonged post-antibiotic effect. Cefoperazone-sulbactam is an attractive candidate for evaluation in the treatment of nosocomial infections due to aerobic gram-negative bacilli.
This study was presented at the 89th Annual Meeting of the American Society for Microbiology held in New Orleans, Louisiana during May 14–18, 1989. 相似文献
In-vitro-Empfindlichkeit cefoperazon-sensibler und -resistenter gramnegativer Stäbchen gegenüber Cefoperazon plus Sulbactam, anderen -Laktamen, Aminoglykosiden und Chinolon
Zusammenfassung Wir führten Vergleichsuntersuchungen zurIn-vitro-Aktivität von Cefoperazon-Sulbactam (2 : 1), anderen -Laktamen, Aminoglykosiden und Ciprofloxacin gegen cefoperazon-empfindliche und -resistente nosokomiale Isolate gramnegativer Bazillen durch. Resistente Isolate einschließlichPseudomonas aeruginosa waren empfindlich gegenüber Cefoperazon-Sulbactam; empfindliche Isolate sprachen auf die Kombination etwas besser an. Sulbactam allein wies nur geringe Aktivität auf. Unter den übrigen geprüften Substanzen waren Ciprofloxacin und Imipenem am wirksamsten. Mit Cefoperazon-Sulbactam war kein Inoculum-Effekt festzustellen. Die Kombination hatte einen anhaltenden postantibiotischen Effekt. Cefoperazon-Sulbactam ist eine interessante Substanzkombination, die in der Therapie nosokomialer Infektionen durch aerobe gramnegative Bazillen erprobt werden sollte.
This study was presented at the 89th Annual Meeting of the American Society for Microbiology held in New Orleans, Louisiana during May 14–18, 1989. 相似文献
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Nirmala Chandrasekar Sanjeeva Mohanam S Sajani Lakka Dzung H Dinh William C Olivero Meena Gujrati Jasti S Rao 《Clinical cancer research》2003,9(6):2342-2349
PURPOSE: Tumor vasculature provides the infrastructure by which malignant tissue can be nourished; therefore, targeting angiogenesis may be an effective means of treating cancer. We showed previously that SNB19 glioblastoma cells modulate bovine retinal endothelial cells in cocultures to form capillary-like network structures, that matrix metalloproteinase-9 (MMP-9) expression is critical for endothelial morphogenesis, and that MMP-9 expression in glioblastoma cells is regulated by extracellular signal-regulated kinase-1 (ERK-1). In the present study, we investigated whether interfering with the activation of this mitogen-activated protein (MAP) kinase would repress MMP-9 synthesis and inhibit capillary formation. EXPERIMENTAL DESIGN: Cocultures of bovine retinal endothelial and SNB19 cells were analyzed for MMP-9 secretion, and phospho- and total ERK levels. These cocultures were treated with PD98059, a specific inhibitor of MAP/ERK kinase 1, or transfected with dominant-negative ERK-1 mutant containing expression vector. Alterations in capillary-like structure formation, and actin cytoskeleton and secretion of vascular endothelial growth factor (VEGF), MMP-9, and tissue inhibitor of metalloproteinase-1 were determined by immunofluorescence, gelatin zymography, and Western blotting. RESULTS: We found that inhibition of the ERK-1/2 pathway with PD98059 abrogated glial cell-mediated capillary formation by the endothelial cells and reduced the levels of MMP-9 in the coculture. Strikingly, the abrogation of MAP kinase signaling by a dominant-negative ERK-1 mutant inhibited glial-induced capillary network formation by reducing VEGF levels and MMP-9 activity and increasing the levels of tissue inhibitor of metalloproteinase-1. Inhibition of ERK activity also disrupted the formation of the actin cytoskeleton, a prerequisite for endothelial cell migration. CONCLUSION: The mechanism underlying activation of ERK is involved in reorganization of the actin cytoskeleton, and induction of VEGF and MMP-9, thereby stimulating endothelial cell morphogenesis. These studies clearly provide experimental evidence that ERK inhibition diminishes glial-induced endothelial-cell morphogenesis; therefore, interfering with ERK signaling may be a viable approach to target angiogenesis. 相似文献
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Veerappan Muthuviveganandavel Inho Hwang Vanattayen Anita Pattabiraman S. Malarani Chandrasekar Selvam Moorthy Hemalatha Muthuraman Pandurangan 《International journal of experimental pathology》2013,94(2):104-108
Alpha‐cypermethrin is an isoform of cypermethrin; it is an active pyrethroid used extensively to control a wide range of pests in agriculture and animal breeding. In this study four groups of six fish were examined. The first group served as a control in fresh water alone, with no pyrethroid. The second, third and fourth groups were exposed to alpha‐cypermethrin for 4, 8 and 96 h respectively. At the end of the each exposure period, the fish were sacrificed, and the required muscle tissues were collected for histological examination. The blood was drawn with heparinized needles and processed for serum enzymatic studies. Serum enzymes such as aspartate transaminase (AST), alanine transaminase (ALT), amylase, acid phosphatase (ACP) and gamma‐glutamyl transpeptidase (GGT) were measured at 4, 8 and 96 h. AST enzyme activity was significantly increased at 4 h, whereas ALT and amylase enzyme activities were significantly reduced at all the time points. ACP enzyme activity was significantly reduced at 4 and 8 h, whereas GGT enzyme activity was significantly increased at all the time points. Hepatocyte cytoplasmic vacuolisation and degeneration, rupture of blood vessels, and necrosis was found at all time points. Congestion of blood vessels, bulging, distortion of filaments, erosion and disintegration of blood corpuscles and hyperplasia of epithelium were found in treated gills at 4, 8 and 96 h. Breakdown of muscle fibres, vacuolation and accumulation of lipids and melanin in white muscle were observed in treated fish muscle at 4, 8 and 96 h. 相似文献
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Vijayakumar Raju Muralidharan Srinivasan Chandrasekar Padmanaban Venkatadevanathan Muthubaskaran Rajpal Kanaklal Abhaichand 《Indian Journal of Thoracic and Cardiovascular Surgery》2011,27(1):36-38
Diagnostic evaluation of embolic neurologic events requires the consideration of cardiac causes. Lambl’s Excrescences (LE)are
filiform fronds that occur at sites of valvular closure due to “wear and tear” (Lambl Wien Med Wschr 6:244–247, 1856). The complex form of LE is “giant Lambl’s Excrescences” which results from the adherence of multiple adjacent excrescences
that grow large. We recently had young male adult who presented with features of posterior circulation stroke (basilar) and
detected to have two separate giant Lambl’s Excrescences on the aortic valve and treated successfully. 相似文献