全文获取类型
收费全文 | 374篇 |
免费 | 39篇 |
国内免费 | 1篇 |
学科分类
医药卫生 | 414篇 |
出版年
2022年 | 3篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 5篇 |
2016年 | 11篇 |
2015年 | 11篇 |
2014年 | 11篇 |
2012年 | 4篇 |
2011年 | 5篇 |
2010年 | 4篇 |
2009年 | 8篇 |
2008年 | 19篇 |
2007年 | 18篇 |
2006年 | 25篇 |
2005年 | 25篇 |
2004年 | 21篇 |
2003年 | 23篇 |
2002年 | 29篇 |
2001年 | 23篇 |
2000年 | 13篇 |
1999年 | 16篇 |
1998年 | 6篇 |
1997年 | 7篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 9篇 |
1991年 | 9篇 |
1990年 | 4篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1981年 | 2篇 |
1978年 | 2篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1970年 | 2篇 |
1969年 | 4篇 |
1932年 | 2篇 |
1925年 | 2篇 |
1920年 | 2篇 |
1912年 | 1篇 |
1906年 | 1篇 |
排序方式: 共有414条查询结果,搜索用时 15 毫秒
41.
The Syrian hamster embryo cell transformation assay has been used to investigate the effect of two synthetic antioxidants on morphological transformation induced by the initiator benzo[a]pyrene (BP). A two-stage protocol was employed with an initiation phase of 2 days and a subsequent promotion phase of 5 days. When 10 microM butylated hydroxytoluene (BHT) were present in the promotion phase instead of the solvent the transformation frequency at 0.1 micrograms BP/ml increased from 0.27% to 0.55%; at 100 microM of BHT the transformation frequency was 0.77%. Butylated hydroxyanisole (BHA) also enhanced the percentage of transformed colonies from 0.40% (10 microM) to 0.49% (100 microM), respectively. No significant initiating activity was detected for both antioxidants when tested in the initiation phase instead of BP; when the antioxidants were applied simultaneously with BP (1 microgram/ml) during the initiation phase the transformation frequency was decreased from 0.64% to 0.15% (100 microM BHT) and to 0.17% (100 microM BHA), respectively. These results show that the dual action of phenolic antioxidants on chemical carcinogenesis, which depends on the administration schedule, can be imitated in an in vitro test system. In addition to their anti-initiation effect, BHT and BHA, while devoid of intrinsic initiator potency, exert a moderate promotional activity on hamster embryo cell cultures. Their ability to enhance tumorigenesis by various carcinogens in vivo is likely to be at least partially related to such promotion-like effects on cell growth and morphology. 相似文献
42.
43.
Moore DF Gelderman MP Ferreira PA Fuhrmann SR Yi H Elkahloun A Lix LM Brady RO Schiffmann R Goldin E 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(19):8065-8070
Fabry disease is a disorder of alpha-D-galactosyl-containing glycolipids resulting from a deficiency of alpha-galactosidase A. Patients have a poorly understood vascular dysregulation. We hypothesized that disease-related perturbation by using enzyme replacement therapy in the murine model of Fabry disease would provide insight into abnormal biological processes in Fabry disease. Gene expression analyses of the heart, aorta, and liver of male alpha-galactosidase A knockout mice 28 weeks of age were compared with that of WT mice. Microarray analyses were performed before and after six weekly injections of alpha-galactosidase A. Alteration of Rpgrip1 ranked highest statistically in all three organs when knockout mice were compared with WT, and its splice variants responded in a unique way to alpha-galactosidase A. Enzyme replacement therapy tended to not only normalize gene expression, e.g., reduce the overexpression of securin, but also specifically modified gene expression in each tissue examined. Following multiple comparison analysis, gene expression correlation graphs were constructed, and a priori hypotheses were examined by using structural equation modeling. This systems biology approach demonstrated multiple and complex parallel cellular abnormalities in Fabry disease. These abnormalities form the basis for informed, in a Bayesian sense, sequential, hypothesis-driven research that can be subsequently tested experimentally. 相似文献
44.
Since 5-fluorouracil (5-FU)-based chemotherapy has become standard adjuvant treatment for patients with node-positive colonic adenocarcinoma, there has arisen the need for predictive factors. Thymidylate synthase (TS) is a major target of 5-FU's action, and high TS expression in carcinoma cells could reduce its cytostatic effect. Both, a 28-base pair repeat polymorphism and a cytosine vs. guanine single nucleotide polymorphism in the promoter region of the TS gene are known to modulate its expression. All patients with a single, non-metachronous node-positive colonic adenocarcinoma who underwent a potentially curative resection at this institution in the years 1994-2002, and who received adjuvant 5-FU (n=95) were included in this study. Ninety-four of the 95 patients were successfully genotyped: 70 patients were classified as TS gene low-expressors (2R-2R, 2R-3C and 3C-3C), and 24 patients were classified as high-expressors (2R-3G, 3C-3G and 3G-3G). Contrary to the hypothesis, Kaplan-Meier survival analysis did not reveal any differences between the groups (power of 0.8 to detect an absolute survival difference >30%). In a Cox model, venous angioinvasion and the infiltrative pattern of tumour invasion were strong adverse factors. These results argue against a practical role for the TS gene repeat polymorphism or the C/G single nucleotide polymorphism as a predictive factor. However, by careful histopathological examination a high-risk group of node-positive patients can be defined that could be candidates for studies of alternative (more aggressive) adjuvant treatment. 相似文献
45.
46.
Sami-Ramzi Leyh-Bannurah Lars Budäus Emanuele Zaffuto Raisa S. Pompe Marco Bandini Alberto Briganti Francesco Montorsi Jonas Schiffmann Shahrokh F. Shariat Margit Fisch Felix Chun Hartwig Huland Markus Graefen Pierre I. Karakiewicz 《Urologic oncology》2018,36(2):81.e17-81.e24
Purpose
To assess adherence rates to pelvic lymph node dissection (PLND) according to National Comprehensive Cancer Network (NCCN) PLND guideline (2% or higher risk) and D’Amico lymph node invasion (LNI) risk stratification (intermediate/high risk) in contemporary North American patients with prostate cancer treated with radical prostatectomy (RP).Material and methods
We relied on 49,358 patients treated with RP and PLND (2010–2013) in SEER database. Adherence rates were quantified and multivariable (MVA) logistic regression analyses tested for independent predictors.Results
According to NCCN PLND guideline and D’Amico LNI classification, PLND was recommended in 63.3% and 64.9% of patients, respectively. Corresponding adherence rates were 68.8% and 69.1%. Adherence rates improved from 67.3% to 71.6% and from 67.6% to 72.0%, respectively, over time. In MVA, more advanced clinical stage, higher biopsy Gleason score and higher number of positive biopsy cores predicted PLNDs that were performed below NCCN LNI nomogram risk threshold. Conversely, lower clinical stage, lower PSA and lower biopsy Gleason score predicted PLND omission in individuals with risk level above NCCN LNI nomogram risk threshold. MVA results for D’Amico classification were virtually identical.Conclusions
Adherence to NCCN PLND guideline and D’Amico LNI classification for purpose of PLND is suboptimal in SEER population-based patients treated with RP. However, adherence rates have improved over time. Patients, who did not undergo PLND despite elevated LNI risk, had more favorable PCa characteristics than the average. Conversely, patients, who underwent PLND despite low-risk, had worse PCa characteristics than the average. 相似文献47.
Identification of pathologically favorable disease in intermediate‐risk prostate cancer patients: Implications for active surveillance candidates selection 下载免费PDF全文
48.
Florian Schiffmann Joost VandeVondele Jürg Hutter Atsushi Urakawa Ronny Wirz Alfons Baiker 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(11):4830-4833
A highly efficient mechanism for the regeneration of the cis-bis(isothiocyanato)bis(2,2′-bipyridyl-4,4′-dicarboxylato)-ruthenium(II) sensitizing dye (N3) by I- in acetonitrile has been identified by using molecular dynamics simulation based on density functional theory. Barrier–free complex formation of the oxidized dye with both I- and , and facile dissociation of and from the reduced dye are key steps in this process. In situ vibrational spectroscopy confirms the reversible binding of I2 to the thiocyanate group. Additionally, simulations of the electrolyte near the interface suggest that acetonitrile is able to cover the (101) surface of anatase with a passivating layer that inhibits direct contact of the redox mediator with the oxide, and that the solvent structure specifically enhances the concentration of I- at a distance which further favors rapid dye regeneration. 相似文献
49.
Glycolysis as primary energy source in tumor cell chemotaxis 总被引:5,自引:0,他引:5
M E Beckner M L Stracke L A Liotta E Schiffmann 《Journal of the National Cancer Institute》1990,82(23):1836-1840
The energy requirements via glycolytic pathways were directly measured in migrating tumor cells. Motility in the metastatic human melanoma cell line A2058, stimulated by insulinlike growth factor I (IGF-I), depends on glycolysis in the presence of glucose as its principal source of energy. Motility in glucose-free medium was 75% reduced and utilized mitochondrial respiration (inhibited by oligomycin). With increasing (physiologic) glucose concentrations, there was a dramatic shift to anaerobic glycolysis as the energy source and 93% elimination of the oligomycin inhibition of motility. Oxamate, an inhibitor of glycolysis, inhibited motility at all glucose concentrations. CO2 production from glycolysis and from the hexose monophosphate shunt was measured in migrating tumor cells. The time course and glucose-dose dependence of glycolytic CO2 production correlated directly with motility. In contrast, mitochondrial CO2 production was inversely related to glucose concentration. A monoclonal antibody for the IGF-I receptor inhibited both motility and glycolytic CO2 production, indicating that both processes are receptor mediated. 相似文献
50.