全文获取类型
收费全文 | 799篇 |
免费 | 54篇 |
国内免费 | 16篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 9篇 |
妇产科学 | 3篇 |
基础医学 | 90篇 |
口腔科学 | 9篇 |
临床医学 | 52篇 |
内科学 | 225篇 |
皮肤病学 | 22篇 |
神经病学 | 50篇 |
特种医学 | 12篇 |
外科学 | 89篇 |
预防医学 | 12篇 |
眼科学 | 1篇 |
药学 | 54篇 |
中国医学 | 1篇 |
肿瘤学 | 239篇 |
出版年
2023年 | 7篇 |
2022年 | 13篇 |
2021年 | 27篇 |
2020年 | 23篇 |
2019年 | 29篇 |
2018年 | 19篇 |
2017年 | 18篇 |
2016年 | 22篇 |
2015年 | 35篇 |
2014年 | 42篇 |
2013年 | 41篇 |
2012年 | 53篇 |
2011年 | 67篇 |
2010年 | 27篇 |
2009年 | 27篇 |
2008年 | 61篇 |
2007年 | 48篇 |
2006年 | 39篇 |
2005年 | 41篇 |
2004年 | 45篇 |
2003年 | 42篇 |
2002年 | 29篇 |
2001年 | 13篇 |
2000年 | 13篇 |
1999年 | 11篇 |
1998年 | 4篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 1篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 1篇 |
1974年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有869条查询结果,搜索用时 656 毫秒
71.
Ikeda S Kurose K Ozawa S Sai K Hasegawa R Komamura K Ueno K Kamakura S Kitakaze M Tomoike H Nakajima T Matsumoto K Saito H Goto Y Kimura H Katoh M Sugai K Minami N Shirao K Tamura T Yamamoto N Minami H Ohtsu A Yoshida T Saijo N Saito Y Sawada J 《Drug metabolism and pharmacokinetics》2003,18(6):413-418
72.
Nakamura Y Kunitoh H Kubota K Sekine I Yamamoto N Tamura T Kodama T Saijo N 《American journal of clinical oncology》2003,26(5):459-464
The efficacy and toxicity of low-dose docetaxel (60 mg/m2) were evaluated in patients with relapsed non-small-cell lung cancer (NSCLC) after platinum-containing chemotherapy. Docetaxel 60 mg/m2 was infused during 1 hour with no routine premedication, with courses repeated at 3-week intervals. Twenty-seven patients were analyzed retrospectively. The median age was 56 years (range, 32-72); 22 patients (81.5%) had adenocarcinoma, 26 (96.3%) had stage IV disease, and 23 (85.2%) were Eastern Cooperative Oncology Group performance status 0 to 1. Five patients (18.5%) had a partial response. Median progression-free survival time for all patients was 1.9 months, and median survival time was 9.4 months. The predominant toxicity was neutropenia, which was grade III or IV in 63% of patients. No neutropenic fever was observed. Other hematologic toxicities were mild (all grade II). Thus, low-dose docetaxel (60 mg/m2) yielded a response rate comparable to that achieved with moderate- to high-dose docetaxel (75-100 mg/m2) as second-line chemotherapy in platinum-pretreated NSCLC, and had less toxicity. Further investigation of the optimal docetaxel dose as second-line chemotherapy in NSCLC is warranted. 相似文献
73.
Tatsumi T Herrem CJ Olson WC Finke JH Bukowski RM Kinch MS Ranieri E Storkus WJ 《Cancer research》2003,63(15):4481-4489
We have evaluated CD8+ and CD4+ T-cell responses against a new tumor-associated antigen, the receptor tyrosine kinase EphA2, which is broadly expressed in diverse cancer histologies and is frequently overexpressed in advanced stage/metastatic disease. We report herein that EphA2 is overexpressed in renal cell carcinoma (RCC) cell lines and clinical specimens of RCC, and find that the highest levels of EphA2 are consistently found in the most advanced stages of the disease. We identified and synthesized five putative HLA class I-binding and three class II-binding peptides derived from EphA2 that might serve as targets for immune reactivity. Each peptide induced specific, tumor-reactive CD8+ or CD4+T-cell responses as measured using IFN-gamma enzyme-linked immunospot assays. The EphA2 peptides elicited relatively weak responses from CD8+ T cells derived from normal healthy volunteers or from RCC patients with active disease. In marked contrast, immune reactivity to EphA2-derived epitopes was greatly enhanced in CD8+ T cells that had been isolated from patients who were rendered disease-free, after surgery. Furthermore, enzyme-linked immunospot analyses demonstrated prominent EphA2-restricted T-helper 1-type CD4+ T cell activity in patients with early stage disease, whereas T-helper 2-type and T regulatory-type responses predominated in patients with more advanced forms of RCC. These data suggest that the immune system of cancer patients actively monitors EphA2-derived epitopes, and that the magnitude and character of T-cell responses to EphA2 epitopes may convey much-needed predictive information about disease stage and outcome. 相似文献
74.
Watanabe H Yamamoto S Kunitoh H Sekine I Yamamoto N Ohe Y Tamura T Kodama T Sugimura K Saijo N 《Cancer science》2003,94(11):1015-1020
We investigated the validity and inter-criteria reproducibility between RECIST (Response Evaluation Criteria in Solid Tumors) guidelines and WHO (World Health Organization) criteria, considering the decrease in patient numbers resulting from inclusion of the minimum lesion size criterion introduced in RECIST guidelines. RECIST guidelines are based on unidimensional measurement and exclusion of small lesions from measurement. The aims of the study were to examine: (1) the effect of the minimum lesion size criterion, (2) the validity of unidimensional and bidimensional measurements, i.e., their relationship with tumor volume, (3) the inter-criteria reproducibility between current RECIST guidelines and previous WHO criteria. One hundred and twenty patients with non-small cell lung cancer (NSCLC) in clinical trials were evaluated. By applying the minimum lesion size criterion, six cases became ineligible without any influence on precision of tumor volume measurement. In the validity study, actual tumor volume was regarded as the gold standard. Although the unidimensional measurement had a lower correlation with tumor volume value than the bidimensional measurement, both the unidimensional measurement and bidimensional measurement correlated sufficiently well with tumor volume changes and the assessed tumor volume response. In the inter-criteria reproducibility study between RECIST guidelines and WHO criteria, the response rate assessed by RECIST guidelines (19.3%) was almost the same as that assessed by WHO criteria (20.0%). In conclusion, RECIST guidelines are adequate for evaluating tumor response to chemotherapy in terms of both validity in relation to tumor volume and inter-criteria reproducibility with the WHO criteria. 相似文献
75.
Takama H Tanaka H Sudo T Tamura T Tanigawara Y 《Cancer chemotherapy and pharmacology》2001,47(5):404-410
PURPOSE: KRN5500, a novel spicamycin derivative, shows the greatest activity against a human tumor xenograft model and the highest therapeutic index among spicamycin derivatives. KRN5500 is currently under clinical development in Japan and the United States. The objective of this study was to develop a population pharmacokinetic model that describes the KRN5500 plasma concentration versus time data. METHODS: Data were collected from 18 patients entered in a phase 1 study. These patients received KRN5500 3-21 mg/m2 as a 2-h infusion. A total of 219 concentration measurements were available. The data were analyzed using the nonlinear mixed effect model (NONMEM) program. In addition, the basic and final population pharmacokinetic models were evaluated using bootstrapping resampling. RESULTS: The basic model selected was a two-compartment model with a combination of additive and constant coefficient of variation error models. The basic model fitted well not only the original data, but also 100 bootstrap replicates generated from the original data set. With regard to the effect of covariates selected by generalized additive modeling analysis, gender (SEX) and performance status were found to be possible determinants of the volume of central compartment by NONMEM analysis. The final regression model for V1 was V1 = theta V1 (1--SEX x theta SEX), where V1 is the typical population value of the volume of central compartment, and SEX = 0 if the patient is male, otherwise SEX = 1. The final model was fitted to the 200 bootstrapped samples. The mean parameter estimates were within 15% of those obtained with the original data set. CONCLUSIONS: The KRN5500 plasma concentration versus time data obtained from the phase 1 study were well described by the population pharmacokinetic model. Further evaluation by bootstrapping showed that the population pharmacokinetic model was stable. 相似文献
76.
77.
A Fukamizu 《Nihon rinsho. Japanese journal of clinical medicine》1999,57(5):1176-1181
This brief review was designed to summarize the relationship between the renin-angiotensin system and arteriosclerosis. Tsukuba hypertensive mice (THM) carrying both the human renin and angiotensinogen genes and C57BL/6J control mice 2 to 3 months of age were fed with either a western or normal diet for 14 weeks. Compared with controls, microscopic analyses revealed accelerated damage of cellular structure in the aortic root in THM fed with the western diet. Remarkably, the surface area of arteriosclerotic lesion in THM was shown to be 4 times larger than that in C57BL/6J on the same western diet. These findings suggested that hypertension induced by the activated renin-angiotensin system is involved in the development of arteriosclerotic lesions. 相似文献
78.
Hisada Y Sugaya T Yamanouchi M Uchida H Fujimura H Sakurai H Fukamizu A Murakami K 《The Journal of clinical investigation》1999,103(5):627-635
Several lines of evidence show the importance of angiotensin II (AII) in renal injuries, especially when hemodynamic abnormalities are involved. To elucidate the role of AII in immune-mediated renal injury, we studied anti-glomerular basement membrane (GBM) nephritis in AII type 1a receptor (AT1a)-deficient homozygous (AT1a-/-) and wild-type (AT1a+/+) mice. A transient activation of the renin-angiotensin system (RAS) was observed in both groups of mice at around day 1. A renal expression of monocyte chemoattractant protein-1 (MCP-1) was transiently induced at six hours in both groups, which was then downregulated at day 1. In the AT1a+/+ mice, after RAS activation, the glomerular expression of MCP-1 was exacerbated at days 7 and 14. Thereafter, severe proteinuria developed, and the renal expressions of transforming growth factor-beta1 (TGF-beta1) and collagen type I increased, resulting in severe glomerulosclerosis and interstitial fibrosis. In contrast, glomerular expression of MCP-1, proteinuria, and tissue damage were markedly ameliorated in the AT1a-/- mice. Because this amelioration is likely due to the lack of AT1a, we can conclude that AII action, mediated by AT1a, plays a pathogenic role in anti-GBM nephritis, in which AII may contribute to the exacerbation of glomerular MCP-1 expression. These results suggest the involvement of AII in immune-mediated renal injuries. 相似文献
79.
80.
Takuya Miyagi Tetsuo Takehara Akio Uemura Kumiko Nishio Satoshi Shimizu Takahiro Kodama Hayato Hikita Wei Li Akira Sasakawa Tomohide Tatsumi Kazuyoshi Ohkawa Tatsuya Kanto Naoki Hiramatsu Norio Hayashi 《Journal of gastroenterology》2010,45(12):1247-1254