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排序方式: 共有1263条查询结果,搜索用时 0 毫秒
41.
T. J. KUNICKI S. A. WILLIAMS D. R. SALOMON P. HARRISON P. CRISLER P. NAKAGAWA T. S. MONDALA S. R. HEAD D. J. NUGENT 《Journal of thrombosis and haemostasis》2009,7(12):2116-2122
Summary. Background: The Platelet Function Analyzer‐100 (PFA‐100) is widely used to measure platelet reactivity in whole blood under high shear. Objective: To characterize the genetic component of platelet reactivity among normal individuals, using the PFA‐100. Methods: We compared baseline platelet reactivity with sex, age, platelet count, hematocrit, plasma von Willebrand factor antigen (VWF:Ag), and alleles of seven candidate genes: integrin subunits α2 (ITGA2) and β3 (ITGB3), platelet glycoproteins GPIbα (GP1BA) and GPVI (GP6), purinogenic receptors (P2RY1 and P2RY12) and cyclooxygenase‐1 (COX1). Results: Based on linear and logistic regression models, we report an inverse correlation between baseline closure time (CT) initiated by collagen plus epinephrine (CEPI) and plasma VWF:Ag level, ITGA2 807T and P2RY1 893C, and an inverse correlation between baseline CT initiated by collagen plus adenosine diphosphate (CADP) and P2RY1 893C or GP1BA ‐5C. Conclusions: These results indicate that genetic polymorphisms in ITGA2 and P2RY1 combine with plasma VWF:Ag levels to modulate baseline platelet reactivity in response to collagen plus EPI, while genetic differences in P2RY1 and GP1BA significantly effect platelet responses to collagen plus ADP. Our results demonstrate that the PFA‐100 can be used to evaluate the effects of genetic predictors of platelet function. 相似文献
42.
Identification and use of biomarkers in Gaucher disease and other lysosomal storage diseases 总被引:1,自引:0,他引:1
J M F G Aerts C E M Hollak M van Breemen M Maas J E M Groener RG Boot 《Acta paediatrica (Oslo, Norway : 1992)》2005,94(S447):43-46
The value of biomarkers in the clinical management of lysosomal storage diseases is best illustrated by the present use of plasma chitotriosidase levels in the diagnosis and monitoring of Gaucher disease. The enzyme chitotriosidase is specifically produced and secreted by the pathological storage macrophages (Gaucher cells). Plasma chitotriosidase levels are elevated on average 1000-fold in symptomatic patients with Gaucher disease and reflect the body burden on storage cells. Changes in plasma chitotriosidase reflect changes in clinical symptoms. Monitoring of plasma chitotriosidase levels is nowadays commonly used in decision making regarding initiation and optimization of costly therapeutic interventions (enzyme replacement therapy or substrate reduction therapy). A novel substrate has been developed that further facilitates the measurement of chitotriosidase in plasma samples. Moreover, an alternative Gaucher-cell marker, CCL18, has been very recently identified and can also be employed to monitor the disease, particularly in those patients lacking chitotriosidase due to a genetic mutation. There is a need for comparable surrogate markers for other lysosomal storage diseases and the search for such molecules is an area of intense investigation.
Conclusion: The use of biomarkers can provide valuable insight into the molecular pathogenesis of LSDs, such as Gaucher disease and Fabry disease. 相似文献
Conclusion: The use of biomarkers can provide valuable insight into the molecular pathogenesis of LSDs, such as Gaucher disease and Fabry disease. 相似文献
43.
Antibodies to tumor necrosis factor alpha prevent increases in cell replication in liver due to the potent peroxisome proliferator, WY- 14,643 总被引:7,自引:6,他引:7
Bojes HK; Germolec DR; Simeonova P; Bruccoleri A; Schoonhoven R; Luster MI; Thurman RG 《Carcinogenesis》1997,18(4):669-674
Several structurally dissimilar hypolipidemic drugs, plasticizers and
halogenated hydrocarbons induce peroxisomes in hepatocytes, and cause
hepatocellular adenoma and carcinoma in rats and mice. The mechanism by
which these agents act is unknown, although recent studies have suggested a
link between increased cell proliferation and hepatic cancer caused by
peroxisome proliferators. Here, we demonstrate that neutralizing antibodies
to tumor necrosis factor alpha (TNF alpha) block increases in protein
kinase C and cell proliferation due to [4-
chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (WY-14,643), a
hypolipidemic drug and potent peroxisome proliferator that causes tumors.
WY-14,643 moderately elevated the level of TNF alpha mRNA in the liver. TNF
alpha was detected immunohistochemically exclusively in Kupffer cells.
These results demonstrate that WY-14,643 acts as an indirect mitogen on
hepatocytes via TNF alpha. We propose that the Kupffer cell, a major source
of TNF alpha in the liver, is involved in the mechanism of the mitogenic
effect of WY-14,643.
相似文献
44.
Evaluation of attempted prevention of unexpected infant death in very high-risk infants by planned health care 总被引:1,自引:0,他引:1
Three hundred and ninety-six babies born in Sheffield between 1982 and 1990 identified as being at "very high risk" of unexpected infant death by means of a scoring system, received an intensive programme of health care including a case discussion between a paediatrician, the GP and the health visitor held in the family doctor's surgery, weekly visits from the health visitor and informal hospital admission. Significantly fewer sudden unexpected infant deaths occurred in this group than were expected by logistic regression anlysis or occurred in the best available control group with comparable scores ( p = 0.024). Problems in evaluation include identification of an adequate control population, ethical difficulties in introducing a controlled study when the programme is already perceived as effective, and the calculation of "expected death rates". The results of this study indicate that very energetic programmes of intervention may prevent some deaths in vulnerable infants. 相似文献
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A method is described for comparing the duration of active respiratoryresponses to irritation of the respiratory tract during anaesthesiawith different agents. The reflex responses were more prolongedwith cyclopropane and thiopentone than with nitrous oxide aloneor halothane with nitrous oxide. Each agent was administeredto five patients. Atropine sulphate 1.2 mg given intravenouslyin five cases before stimulation, failed to modify the responsesduring cyclopropane anaesthesia. The differences in the durationsof response are unexplained. It is suggested that they are determinedby the strength and duration of the stimulus, and by the effectof the anaesthetic agent on the sensitivities of the reflexarc and the respiratory centre.
* At present at the Department of Anesthesia, Western ReserveUniversity, Cleveland, Ohio. 相似文献
49.