全文获取类型
收费全文 | 1543篇 |
免费 | 136篇 |
国内免费 | 2篇 |
专业分类
1681篇 |
出版年
2023年 | 8篇 |
2022年 | 11篇 |
2021年 | 33篇 |
2020年 | 28篇 |
2019年 | 26篇 |
2018年 | 31篇 |
2017年 | 36篇 |
2016年 | 47篇 |
2015年 | 80篇 |
2014年 | 61篇 |
2013年 | 99篇 |
2012年 | 150篇 |
2011年 | 120篇 |
2010年 | 79篇 |
2009年 | 68篇 |
2008年 | 93篇 |
2007年 | 82篇 |
2006年 | 78篇 |
2005年 | 79篇 |
2004年 | 74篇 |
2003年 | 56篇 |
2002年 | 65篇 |
2001年 | 24篇 |
2000年 | 24篇 |
1999年 | 20篇 |
1998年 | 22篇 |
1997年 | 19篇 |
1996年 | 11篇 |
1995年 | 18篇 |
1994年 | 12篇 |
1993年 | 12篇 |
1992年 | 16篇 |
1991年 | 11篇 |
1990年 | 12篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 9篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1981年 | 2篇 |
1979年 | 8篇 |
1978年 | 7篇 |
1976年 | 2篇 |
1975年 | 6篇 |
1968年 | 3篇 |
1960年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有1681条查询结果,搜索用时 15 毫秒
101.
102.
Matthew G. Stanton Jed Hubbs David Sloman Christopher Hamblett Paula Andrade Minilik Angagaw Grace Bi Regina M. Black Jamie Crispino Jonathan C. Cruz Eric Fan Georgia Farris Bethany L. Hughes Candia M. Kenific Richard E. Middleton George Nikov Peter Sajonz Sanjiv Shah Nirah Shomer Alexander A. Szewczak Benito Munoz 《Bioorganic & medicinal chemistry letters》2010,20(2):755-758
We report herein a novel series of difluoropiperidine acetic acids as modulators of γ-secretase. Synthesis of 2-aryl-3,3-difluoropiperidine analogs was facilitated by a unique and selective β-difluorination with Selectfluor®. Compounds 1f and 2c were selected for in vivo assessment and demonstrated selective lowering of Aβ42 in a genetically engineered mouse model of APP processing. Moreover, in a 7-day safety study, rats treated orally with compound 1f (250 mg/kg per day, AUC0–24 = 2100 μM h) did not exhibit Notch-related effects. 相似文献
103.
104.
Paloma Moreno Moreno Carmen Gutiérrez Alcántara María del Carmen Muñoz-Villanueva Rafael Palomares Ortega María del Sierra Corpas Jiménez Luis Zurera Tendero Pedro Benito López 《Endocrinología y nutrición》2010,57(3):95-99
Background and objectiveThe aim of this study was to assess the utility of arterial calcium stimulation with hepatic venous sampling (ASVS) in the localization of tumors in patients with endogenous hyperinsulinism not detected with other methods.Patients and methodsWe performed a retrospective study of 26 patients admitted to our hospital for hypoglycemia who underwent ASVS because the source of hyperinsulinism was not clearly identified by other imaging techniques. The histopathological result in patients who underwent a surgical procedure was considered the reference for statistical study of the accuracy of this technique. Statistical analysis was performed by comparing proportions with the chi-squared test with Yates’ correction for contingency tables, and Cohen′s kappa coefficient as a measure of interrater agreement between two observations.ResultsSurgery was performed in 17 patients, 13 with positive ASVS and the remaining four with negative results. An insulinoma was removed in 12 patients, and 10 of these were detected in the ASVS. A total of 76.9 % of positive ASVS tests corresponded to a histological diagnosis of insulinoma, and 83% of these insulinomas were positive in ASVS. This association was statistically significant (chi cuadrado = 7.340; p = 0.012). Two of three patients with nesidioblastosis had a positive response in the ASVS. A good and statistically significant agreement was obtained between histopathologic diagnosis and ASVS results (κ=0.556, p = 0.007).ConclusionsASVS is a useful procedure in the localization diagnosis of endogenous hyperinsulinism not detected by other imaging tests. This technique allows tumors in the pancreatic gland to be identified and may be useful in the choice of the surgical technique to be used. 相似文献
105.
Francisco Guil Sandra Agudín Nuria El-Khadir Mariana Fernandez-Olalla Juan Figueredo Francisco G. Domínguez Paloma Garzon Gregorio Gonzalez Jaime Muñoz-Igualada Javier Oria Fernando Silvestre 《European Journal of Wildlife Research》2010,56(4):633-640
Camera trapping is the most used method for surveying medium-sized carnivores in Spain. The main target for these surveys has been the Iberian lynx, the most endangered cat in the world. The Iberian lynx conservation program has received the largest EU LIFE projects grant. So, efficiency is a key goal for managing this grant. During 2003 and 2007, we have applied these funds to the survey of the Iberian lynx in Eastern Sierra Morena (Spain). Using two different techniques, we have studied both to see which is the most efficient. The survey developed in active latrines resulted more efficient than that of scent stations and live prey camera trapping throughout the years, although there has been a variation between years. Otherwise, the live prey method has been the one providing the greatest speed and number of pictures per entrance. We suggest that camera-trapping surveys can be improved in terms of efficiency for a wide range of species, or at least for the Iberian lynx. To improve the results, cameras might be placed in relation to breeding territories. With this determinant, camera-trapping surveys would be shorter than 120 days. Finally, we suggest how those surveys for medium carnivores should be designed. 相似文献
106.
107.
Sara Rodríguez-Acebes Nuria Palacios José I Botella-Carretero Nuria Olea Lorena Crespo Roberto Peromingo Diego Gómez-Coronado Miguel A Lasunción Clotilde Vázquez Javier Martínez-Botas 《BMC medical genomics》2010,3(1):1-15
Background
Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP) and Triglyceride (TG) (LAT) vs High ASP and TG (HAT). Subcutaneous (SC) and omental (OM) adipose tissues (n = 21) were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined.Methods
LAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1). ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p < 0.01 each). Differences between LAT and HAT group were almost exclusively in SC tissue, with little difference in OM tissue. Increased C5L2 (p < 0.01), an ASP receptor, in HAT suggests a compensatory ASP pathway, associated with increased TG storage.Results
HAT adipose tissue demonstrated increased lipid related genes for storage (CD36, DGAT1, DGAT2, SCD1, FASN, and LPL), lipolysis (HSL, CES1, perilipin), fatty acid binding proteins (FABP1, FABP3) and adipocyte differentiation markers (CEBPα, CEBPβ, PPARγ). By contrast, oxidation related genes were decreased (AMPK, UCP1, CPT1, FABP7). HAT subjects had increased anti-inflammatory genes TGFB1, TIMP1, TIMP3, and TIMP4 while proinflammatory PIG7 and MMP2 were also significantly increased; all genes, p < 0.025.Conclusion
Taken together, the profile of C5L2 receptor, ASP gene expression and metabolic factors in adipose tissue from morbidly obese HAT subjects suggests a compensatory response associated with the increased plasma ASP and TG. 相似文献108.
O. Dauwalder A. -M. Freydière H. Meugnier Y. Benito M. Chomarat C. Ginevra P. Girardo M. -E. Reverdy J. Etienne G. Lina F. Vandenesch 《Bio Tribune Magazine》2010,36(1):6-11
Concomitant chemoradiotherapy can constitute an alternative to surgical approach in selected patients with bladder carcinoma. TNM staging, histological grading, renal and performance status represent the main prognostic factors useful to define the therapeutic strategy. Biological and genetic factors are still controversial in medical practice. The activation of oncogenes seems to characterize the initiation of superficial lowgrade tumors and the mutations in the tumor suppressor genes (TEN, TP53 and RB) appear as the most important biological features in the in situ and invasive tumors. The expression of p53, Rb, Bcl-2 has an obvious prognostic role but the published studies on molecular factors predictive of radiosensibility are heterogeneous. 相似文献
109.
Catenations between sister chromatids result from DNA replication and must be resolved to ensure proper chromatid segregation in mitosis. Functionally active Topoisomerase II (Topo II), through its mechanism of concerted breaking and rejoining of double stranded DNA, is required to carry out this fundamental process. In previous studies we have shown that modifications in DNA sequence by halogenated pyrimidines and by the demethylating agent 5-azacytidine leads to malfunction of Topo II that results in an increased yield of endorreduplicated cells as a result of segregation failure. In the present work we have evaluated the possible influence of the methylating agent Budesonide to modify the frequency of endoreduplicated cells in AA8 Chinese hamster cell population. Our results seem to indicate that when Budesonide was administered for two consecutive cell cycles did induce an increase in the yield of endoreduplicated cells, as previously observed for the hypomethylating agent 5-azaC. We have also examined the possible relationship between extensive hypermethylation induced by Budesonide in DNA and stabilization of cleavable complexes by m-AMSA. Taken as a whole, our results show that the degree of methylation in DNA correlates with the effectiveness of m-AMSA to stabilize the Topo II-DNA complexes and to induce DNA cleavage. These findings evidence for the first time the functional importance of DNA hyper- and hypomethylation changes as epigenetic factors able to modulate Topo II activity for proper chromosome segregation. 相似文献
110.
Victoria Álvarez Elena Sánchez-Ferrero Christian Beetz Marta Díaz Belén Alonso Ana I Corao Josep Gámez Jesús Esteban Juan F Gonzalo Samuel I Pascual-Pascual Adolfo López de Munain Germán Moris Renne Ribacoba Celedonio Márquez Jordi Rosell Rosario Marín Maria J García-Barcina Emilia del Castillo Carmen Benito Eliecer Coto 《BMC neurology》2010,10(1):1-9