全文获取类型
收费全文 | 661篇 |
免费 | 23篇 |
国内免费 | 4篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 4篇 |
妇产科学 | 24篇 |
基础医学 | 135篇 |
口腔科学 | 7篇 |
临床医学 | 53篇 |
内科学 | 59篇 |
皮肤病学 | 120篇 |
神经病学 | 52篇 |
特种医学 | 34篇 |
外科学 | 40篇 |
综合类 | 7篇 |
预防医学 | 54篇 |
眼科学 | 8篇 |
药学 | 56篇 |
中国医学 | 2篇 |
肿瘤学 | 32篇 |
出版年
2023年 | 1篇 |
2022年 | 9篇 |
2021年 | 27篇 |
2020年 | 8篇 |
2019年 | 7篇 |
2018年 | 17篇 |
2017年 | 13篇 |
2016年 | 10篇 |
2015年 | 20篇 |
2014年 | 30篇 |
2013年 | 25篇 |
2012年 | 53篇 |
2011年 | 64篇 |
2010年 | 38篇 |
2009年 | 33篇 |
2008年 | 36篇 |
2007年 | 54篇 |
2006年 | 59篇 |
2005年 | 39篇 |
2004年 | 35篇 |
2003年 | 42篇 |
2002年 | 25篇 |
2001年 | 6篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1997年 | 4篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有688条查询结果,搜索用时 15 毫秒
1.
Eugen Musch Mouhamad Malek Jasna Peter-Katalinic Heinz Egge Hermann Rink Bernd Lathan Eberhard Riedel 《Cancer chemotherapy and pharmacology》1992,29(4):297-304
Summary Intracellular concentrations of prednimustine (PM), chlorambucil (CLB), phenylacetic acid mustard (PAAM) and prednisolone (P) were measured in different experimental tumor cell lines that had been incubated with either PM or CLB+P. For intracellular analytical determination, we modified a high-pressure liquid chromatographic method for the detection of these substances in plasma. Intact PM could be detected in the intracellular compartment of the incubated tumor cells. PM-incubated cells from PM-injected rats exhibited a higher intracellular concentration-time integral (PAAM) and longer concentration-time profiles for drugs with alkylating capacity than did cells exposed to the CLB+P mixture or to CLB. PAAM was not detectable after incubation of cells with PM, whereas in CLB-incubated cells the AUC of PAAM exceeded that of the parent drug CLB. Our in vitro results therefore favour the concept of a facilitated intracellular uptake and an increased antiproliferative effect for PM versus CLB and CLB+P.Dedicated to Prof. Dr. H. J. Dengler on the occasion of his 65th birthday. This study was supported by the Ministry of Science and Research of Nordrhein-Westfalen 相似文献
2.
3.
Jasna E. Deluce Luisa Cardenas Aly-Khan Lalani Saman Maleki Vareki Ricardo Fernandes 《Current oncology (Toronto, Ont.)》2022,29(7):5054
Prostate cancer remains one of the leading causes of cancer death in men worldwide. In the past decade, several new treatments for advanced prostate cancer have been approved. With a wide variety of available drugs, including cytotoxic agents, androgen receptor axis-targeted therapies, and alpha-emitting radiation therapy, identifying their optimal sequencing remains a challenge. Progress in the understanding of the biology of prostate cancer has provided an opportunity for a more refined and personalized treatment selection process. With the advancement of molecular sequencing techniques, genomic precision through the identification of potential treatment targets and predictive biomarkers has been rapidly evolving. In this review, we discussed biomarker-driven treatments for advanced prostate cancer. First, we presented predictive biomarkers for established, global standard treatments for advanced diseases, such as chemotherapy and androgen receptor axis-targeted agents. We also discussed targeted agents with recent approval for special populations, such as poly ADP ribose polymerase (PARP) inhibitors in patients with metastatic castrate-resistant prostate cancer with homologous recombination repair-deficient tumors, pembrolizumab in patients with high levels of microsatellite instability or high tumor mutational burden, and prostate-specific membrane antigen (PSMA) directed radioligand theragnostic treatment for PSMA expressing tumors. Additionally, we discussed evolving treatments, such as cancer vaccines, chimeric antigen receptor T-cells (CAR-T), Bispecific T-cell engagers (BiTEs), other targeted agents such as AKT inhibitors, and various combination treatments. In summary, advances in molecular genetics have begun to propel personalized medicine forward in the management of advanced prostate cancer, allowing for a more precise, biomarker-driven treatment selection with the goal of improving overall efficacy. 相似文献
4.
Hsu HH Hoffmann S Di Marco GS Endlich N Peter-Katalinić J Weide T Pavenstädt H 《Kidney international》2011,80(9):959-969
Podocytes have a significant role in establishing selective permeability of the glomerular filtration barrier. Sustained renin-angiotensin-aldosterone system activation is crucial to the pathogenesis of podocyte injury, but the mechanisms by which angiotensin II modulates podocyte survival due to physiological or injurious stimuli remain unclear. Here, we used proteomic analysis to find new mediators of angiotensin II-induced podocyte injury. Antioxidant protein peroxiredoxin 2 expression was decreased in cultured podocytes stimulated with angiotensin II. Peroxiredoxin 2 was found to be expressed in podocytes in vivo, and its expression was decreased in the glomeruli of rats transgenic for angiotensin II type 1 receptors in a podocyte-specific manner, or in rats infused with angiotensin II. Downregulation of peroxiredoxin 2 in podocytes resulted in increased reactive oxygen species release, protein overoxidation, and inhibition of the Akt pathway. Both treatment with angiotensin II and downregulation of peroxiredoxin 2 expression led to apoptosis of podocytes. Thus, peroxiredoxin 2 is an important modulator of angiotensin II-induced podocyte injury. 相似文献
5.
BACKGROUND: Cardioprotective effects of volatile anesthetics in anesthetic-induced preconditioning involve activation of the cardiac sarcolemmal adenosine triphosphate-sensitive potassium (sarcKATP) channels. This study addressed the memory phase of anesthetic preconditioning by investigating whether brief exposure to isoflurane produces lasting sensitization of the sarcKATP channel and whether protein kinase C mediates this effect. METHODS: Whole cell sarcKATP channel current (IKATP) was monitored from single isolated rat ventricular cardiomyocytes. Pinacidil was used to open the channel, and the magnitude of activated IKATP was an indicator of channel's ability to open. Involvement of protein kinase C was investigated using chelerythrine and isoform-specific peptide inhibitors and activators of protein kinase C-delta and protein kinase C-epsilon. RESULTS: The mean density of IKATP elicited by pinacidil (5 microm) in anesthetic-free conditions was 3.8 +/- 3.7 pA/pF (n = 11). After 10 min of exposure to isoflurane (0.56 mm) and 10 or 30 min of anesthetic washout, pinacidil-elicited IKATP was increased to 15.6 +/- 11.3 pA/pF (n = 12; P < 0.05) and 11.8 +/- 3.9 pA/pF (n = 6; P < 0.05), respectively. In the presence of chelerythrine (5 microm), isoflurane did not potentiate channel opening, and IKATP was 6.6 +/- 4.6 pA/pF (n = 11). Application of protein kinase C-delta peptide inhibitor also abolished isoflurane-induced sensitization of sarcKATP channel, and IKATP was 7.7 +/- 5.4 pA/pF (n = 12). In contrast, protein kinase C-epsilon peptide inhibitor did not affect channel sensitization, and pinacidil-elicited current was 14.8 +/- 9.6 pA/pF (n = 12). Interestingly, when both protein kinase C-delta and protein kinase C-epsilon activators were applied instead of isoflurane, they sensitized the channel to the same extent as isoflurane (18.9 +/- 7.2 pA/pF, n = 11, and 18.6 +/- 11.1 pA/pF, n = 10, respectively). CONCLUSION: Isoflurane induces prolonged sensitization of the sarcKATP channel to opening that persists even after anesthetic withdrawal. Our results indicate that protein kinase C-delta, rather than protein kinase C-epsilon, is a likely mediator of isoflurane effects, although both protein kinase C-delta and protein kinase C-epsilon can modulate the channel function. 相似文献
6.
7.
8.
Tom Platteau Katrien Fransen Ludwig Apers Chris Kenyon Laura Albers Tine Vermoesen Jasna Loos Eric Florence 《Journal of medical Internet research》2015,17(9)
Background
As HIV remains a public health concern, increased testing among those at risk for HIV acquisition is important. Men who have sex with men (MSM) are the most important group for targeted HIV testing in Europe. Several new strategies have been developed and implemented to increase HIV-testing uptake in this group, among them the Swab2know project.Objective
In this project, we aim to assess the acceptability and feasibility of outreach and online HIV testing using oral fluid samples as well as Web-based delivery of test results.Methods
Sample collection happened between December 2012 and April 2014 via outreach and online sampling among MSM. Test results were communicated through a secured website. HIV tests were executed in the laboratory. Each reactive sample needed to be confirmed using state-of-the-art confirmation procedures on a blood sample. Close follow-up of participants who did not pick up their results, and those with reactive results, was included in the protocol. Participants were asked to provide feedback on the methodology using a short survey.Results
During 17 months, 1071 tests were conducted on samples collected from 898 men. Over half of the samples (553/1071, 51.63%) were collected during 23 outreach sessions. During an 8-month period, 430 samples out of 1071 (40.15%) were collected from online sampling. Additionally, 88 samples out of 1071 (8.22%) were collected by two partner organizations during face-to-face consultations with MSM and male sex workers. Results of 983 out of 1071 tests (91.78%) had been collected from the website. The pickup rate was higher among participants who ordered their kit online (421/430, 97.9%) compared to those participating during outreach activities (559/641, 87.2%; P<.001). MSM participating during outreach activities versus online participants were more likely to have never been tested before (17.3% vs 10.0%; P=.001) and reported more sexual partners in the 6 months prior to participation in the project (mean 7.18 vs 3.23; P<.001). A total of 20 participants out of 898 (2.2%) were confirmed HIV positive and were linked to care. Out of 1071 tests, 28 (2.61%) with a weak reactive result could not be confirmed, and were thereby classified as false reactive results. Most of the 388 participants who completed posttest surveys (388/983, 39.5%) were very positive about their experience. The vast majority (371/388, 95.6%) were very satisfied, while 17 out of 388 (4.4%) reported mixed feelings.Conclusions
Despite a high yield and a considerable number of false reactive results, satisfaction was high among participants. The project helped us to reach the target population, both in numbers of tests executed and in newly diagnosed HIV infections. Further optimization should be considered in the accuracy of the test, the functionalities of the website (including an online counseling tool), and in studying the cost effectiveness of the methodology. 相似文献9.
10.
Psychological consequences of war trauma and postwar social stressors in women in Bosnia and Herzegovina 总被引:2,自引:2,他引:0 下载免费PDF全文