全文获取类型
收费全文 | 8566篇 |
免费 | 785篇 |
国内免费 | 468篇 |
专业分类
耳鼻咽喉 | 80篇 |
儿科学 | 97篇 |
妇产科学 | 114篇 |
基础医学 | 992篇 |
口腔科学 | 207篇 |
临床医学 | 1019篇 |
内科学 | 1516篇 |
皮肤病学 | 272篇 |
神经病学 | 553篇 |
特种医学 | 247篇 |
外国民族医学 | 3篇 |
外科学 | 952篇 |
综合类 | 1063篇 |
现状与发展 | 1篇 |
一般理论 | 1篇 |
预防医学 | 554篇 |
眼科学 | 238篇 |
药学 | 881篇 |
5篇 | |
中国医学 | 361篇 |
肿瘤学 | 663篇 |
出版年
2024年 | 16篇 |
2023年 | 117篇 |
2022年 | 266篇 |
2021年 | 373篇 |
2020年 | 253篇 |
2019年 | 282篇 |
2018年 | 326篇 |
2017年 | 270篇 |
2016年 | 274篇 |
2015年 | 383篇 |
2014年 | 421篇 |
2013年 | 461篇 |
2012年 | 584篇 |
2011年 | 652篇 |
2010年 | 386篇 |
2009年 | 305篇 |
2008年 | 458篇 |
2007年 | 479篇 |
2006年 | 508篇 |
2005年 | 455篇 |
2004年 | 303篇 |
2003年 | 308篇 |
2002年 | 213篇 |
2001年 | 182篇 |
2000年 | 182篇 |
1999年 | 196篇 |
1998年 | 136篇 |
1997年 | 120篇 |
1996年 | 89篇 |
1995年 | 82篇 |
1994年 | 69篇 |
1993年 | 38篇 |
1992年 | 99篇 |
1991年 | 58篇 |
1990年 | 69篇 |
1989年 | 35篇 |
1988年 | 53篇 |
1987年 | 49篇 |
1986年 | 39篇 |
1985年 | 35篇 |
1984年 | 20篇 |
1983年 | 17篇 |
1982年 | 13篇 |
1981年 | 20篇 |
1980年 | 11篇 |
1979年 | 21篇 |
1976年 | 15篇 |
1973年 | 9篇 |
1969年 | 7篇 |
1965年 | 6篇 |
排序方式: 共有9819条查询结果,搜索用时 0 毫秒
11.
Increased expression of certain glutathione S-transferase (GST) isoenzymes has frequently been associated with the development of resistance to alkylating agents and other classes of antineoplastic drugs in drug-selected cell lines. The question arises whether this phenomenon is causal or is a stress-induced response associated with drug resistance in these cell lines. We have constructed mammalian expression vectors containing the human GST mu and GST alpha 2 (Ha2) cDNAs and stably transfected them into the human breast cancer cell line MCF-7. Whereas the parental and pSV2neo-transfected cell lines display low GST activity, three individual transfected clones were identified in each group that expressed either GST mu or GST alpha 2. The range of GST activities was similar to those observed in cells selected for anticancer drug resistance. The GST mu specific activities were 56, 150, and 340 mlU/mg, compared with 10 mlU/mg of endogenous GST mu in control lines. Specific activities in GST alpha 2-transfected clones were 17, 28, and 52 mlU/mg, compared with no detectable alpha class GST in control lines. These clonal lines and the parental and pSV2neo-transfected control lines were tested for sensitivity to antineoplastic agents and other cytotoxic compounds. The clones with the highest activity in each group were 1.7-fold (GST alpha 2) to 2.1-fold (GST mu) resistant to the toxic effects of ethacrynic acid, a known substrate for GSTs. However, the GST-transfected cell lines were not resistant to doxorubicin, L-phenylalanine mustard, bis(2-chloroethyl)-1-nitrosourea, cisplatin, chlorambucil, or the GST substrates 1-chloro-2,4-dinitrobenzene or tert-butyl hydroperoxide. Thus, although L-phenylalanine mustard, bis(2-chloroethyl)-1-nitrosourea, chlorambucil, tert-butyl hydroperoxide, and 1-chloro-2,4-dinitrobenzene are known to be metabolized by glutathione-dependent GST-catalyzed reactions, there was no protection against any of these agents in MCF-7 cell lines overexpressing GST mu or GST alpha 2. We conclude that, at the levels of GST obtained in this transfection model system, overexpression of GST mu or GST alpha 2 is not by itself sufficient to confer resistance to these anticancer agents. These studies do not exclude the possibility that GST may be a marker of drug resistance or that other gene products not expressed in MCF-7 cells might cooperate with GST to confer drug resistance. 相似文献
12.
Age and gender related changes in stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil. 总被引:2,自引:2,他引:0 下载免费PDF全文
S K Gupta L Atkinson T Tu J A Longstreth 《British journal of clinical pharmacology》1995,40(4):325-331
1. Pharmacokinetics and pharmacodynamics of R- and S-verapamil and R- and S-norverapamil were studied at steady state following administration of 180 mg verapamil delivered by a controlled-release gastrointestinal therapeutic system (COER-verapamil). 2. Of the 30 young (19 to 43 years) and 30 elderly subjects (65 to 80 years) enrolled, approximately half of each age group were women; all subjects were healthy and none were smokers. 3. Mean R- and S-verapamil and R- and S-norverapamil Cmax, Cmin, and AUC values for elderly subjects were 1.2 to 2.2 times greater than those for young subjects; these differences were statistically significant at P < 0.05. Median tmax values for young and elderly subjects were not significantly different for any enantiomer. The mean half-life values of R- and S-verapamil for elderly subjects were approximately 20 h compared with approximately 13 h for young subjects, respectively. The mean half-life values of R- and S-norverapamil for elderly subjects were approximately 31 h and 20 h, respectively, compared with approximately 19 h and 21 h for young subjects, respectively. 4. In both age groups, the mean plasma verapamil concentrations of each enantiomer were higher for women than for men at all time points. 5. Mean arterial pressure (MAP) had a significant correlation to R- (r2 = 0.86) and S-verapamil (r2 = 0.87) concentration values that was not influenced by either gender or age of the patient. Change in PR-interval also had a significant correlation to R- and S-verapamil concentration values. However, the sensitivity of the response to changes in R- and S-verapamil concentration values in elderly subjects was about 1/5 of that in younger subjects. 相似文献
13.
14.
John Goffin Stefan Baral Dongsheng Tu Dora Nomikos Lesley Seymour 《Clinical cancer research》2005,11(16):5928-5934
PURPOSE: Tumor responses in early-phase trials are used to determine whether new agents warrant further study. Given that spontaneous regressions are observed in melanoma and renal cell carcinoma, this study assessed whether tumor responses, particularly in these two tumor types, predict for future regulatory drug approval. EXPERIMENTAL DESIGN: The literature was reviewed to assess tumor response rates to cytotoxic agents in phase I and II trials in the following solid tumors: melanoma, renal cell carcinoma, non-small-cell lung cancer, breast cancer, ovarian cancer, colorectal cancer, and other solid tumors. Response rates were categorized and the relationship of these categories to the end point of regulatory drug approval was determined. RESULTS: Fifty-eight drugs were assessed in 100 phase I trials, and 46 of these drugs were also studied in 499 phase II trials. Higher overall response rates in both phase I trials (P = 0.03) and phase II trials (P < 0.0001) were predictive of regulatory approval. However, response in melanoma or renal cell carcinoma was not predictive for either phase I or phase II studies. CONCLUSIONS: For cytotoxic agents, although overall objective response rates reliably predict subsequent marketing approval, isolated responses in melanoma and renal cell carcinoma are not predictive. 相似文献
15.
笔者通过对35例阻塞怀黄疸的CT所见,指出了胆道扩张征象可作为鉴别肝内、阻阻塞性黄疸的可靠指标,再结合临床及CT的初期征象,可更加提高其鉴别诊断准确率。本文对这些指标的可靠性进行重点讨论。提出了该特点是特别胆道管囊肿的重要指征,即后者的胆道扩张为局部性或节段性。本文对良、恶性病变所致的胆道扩张形态亦进行了对照分析,发现二阻之间无明显性差异。 相似文献
16.
Chih-Hung Chien Tzong-Yang Tu Shu-Feng Chien Angela Chung-I Li Mei-Jan Yang An-Suey Shiao Yi-Fen Wang 《台湾医志》2006,105(10):832-838
BACKGROUND/PURPOSE: In the geriatric population, the reliability of pure-tone threshold (PTT) is sometimes poorer than that in young adults because of various reasons. This study assessed the relationship between Mandarin speech reception thresholds (SRTs) and PTTs in the aged and developed SRT as a measure for corroborating PTT. METHODS: This prospective study enrolled 46 consecutive subjects over 60 years of age. The results of SRT and PTT were collected from one ear randomly selected from each subject. Simple linear and multiple regressions were used to determine the correlation and linear regression coefficients between SRTs and PTTs at various frequencies. RESULTS: In the simple regression analysis, the correlation coefficient was highest at 1000 Hz (r = 0.949) and 500 Hz (r = 0.922), followed by 250 Hz (r = 0.850) and 2000 Hz (r = 0.792). In the multiple regression model with SRT as the dependent variable and PTTs as predictor variables, the resultant multiple correlation coefficient R was 0.967, while R2 was 0.936. In this model, PTTs at the frequencies of 500 Hz and 1000 Hz contributed significantly to the variance in SRTs with p values of 0.029 and < 0.001, respectively. These results demonstrated that the Mandarin SRT is strongly associated with PTTs at the frequencies of 500 Hz and 1000 Hz. CONCLUSION: This study established the agreement between Mandarin SRTs and PTTs in the low tone area of speech frequencies in the geriatric population. In clinical settings, SRT test can be rapidly and easily performed and is relatively inexpensive. It is a vital indicator of the accuracy of PTT measurement. 相似文献
17.
18.
19.
20.
用基因工程重组的丙肝抗原包被于硝酸纤维素膜,建立了检测丙肝IgG抗体的斑点免疫渗滤法。与ELISA试剂盒进行双盲式同步测定,二法检验结果差异无显著性。渗滤法简便快速,适用于各级医院,有很强的推广价值。 相似文献