全文获取类型
收费全文 | 5042篇 |
免费 | 434篇 |
国内免费 | 6篇 |
学科分类
医药卫生 | 5482篇 |
出版年
2023年 | 29篇 |
2022年 | 38篇 |
2021年 | 95篇 |
2020年 | 60篇 |
2019年 | 85篇 |
2018年 | 112篇 |
2017年 | 99篇 |
2016年 | 118篇 |
2015年 | 117篇 |
2014年 | 158篇 |
2013年 | 232篇 |
2012年 | 337篇 |
2011年 | 379篇 |
2010年 | 210篇 |
2009年 | 169篇 |
2008年 | 320篇 |
2007年 | 383篇 |
2006年 | 405篇 |
2005年 | 345篇 |
2004年 | 307篇 |
2003年 | 266篇 |
2002年 | 257篇 |
2001年 | 75篇 |
2000年 | 75篇 |
1999年 | 77篇 |
1998年 | 42篇 |
1997年 | 29篇 |
1996年 | 34篇 |
1995年 | 31篇 |
1994年 | 21篇 |
1993年 | 21篇 |
1992年 | 36篇 |
1991年 | 37篇 |
1990年 | 30篇 |
1989年 | 30篇 |
1988年 | 28篇 |
1987年 | 23篇 |
1986年 | 35篇 |
1985年 | 37篇 |
1984年 | 27篇 |
1983年 | 20篇 |
1982年 | 20篇 |
1979年 | 30篇 |
1978年 | 15篇 |
1977年 | 16篇 |
1976年 | 15篇 |
1975年 | 20篇 |
1974年 | 19篇 |
1973年 | 18篇 |
1972年 | 15篇 |
排序方式: 共有5482条查询结果,搜索用时 15 毫秒
61.
Nygren P Hande K Petty KJ Fedgchin M van Dyck K Majumdar A Panebianco D de Smet M Ahmed T Murphy MG Gottesdiener KM Cocquyt V van Belle S 《Cancer chemotherapy and pharmacology》2005,55(6):609-616
Background Aprepitant is a selective neurokinin-1 receptor antagonist that is effective for the prevention of nausea and vomiting caused by highly emetogenic chemotherapy. In vitro, aprepitant is a moderate inhibitor of the CYP3A4 enzyme, which is involved in the clearance of several chemotherapeutic agents. In this study we examined the potential for aprepitant to affect the pharmacokinetics and toxicity of intravenously administered docetaxel, a chemotherapeutic agent that is primarily metabolized by CYP3A4.Methods A total of 11 cancer patients (4 male, 7 female, aged 50–68 years) were enrolled in this multicenter, randomized, open-label, two-period, crossover study. Patients received a single infusion of docetaxel monotherapy, 60–100 mg/m2, on two occasions at least 3 weeks apart. During one of the cycles (treatment A), patients received docetaxel alone. During the alternate cycle (treatment B), they also received aprepitant 125 mg orally 1 h prior to docetaxel infusion (day 1), and a single oral dose of aprepitant 80 mg on days 2 and 3. The pharmacokinetic profile of docetaxel was assessed over 30 h following docetaxel infusion. Blood counts were monitored on days 1, 4, 7, and 14.Results Ten patients completed the study. Concomitant administration of aprepitant did not cause any statistically or clinically significant changes in docetaxel pharmacokinetics. Values for docetaxel alone (treatment A) versus docetaxel with aprepitant (treatment B) were as follows: geometric mean AUC0–last was 3.26 vs 3.17 g h/ml (P>0.25; ratio B/A 0.97); geometric mean AUC0– 3.51 vs 3.39 g h/ml (P>0.25; ratio B/A 0.96); geometric mean Cmax was 3.53 vs 3.37 g/ml (P>0.25; ratio B/A 0.95); and geometric mean plasma clearance was 23.3 vs 24.2 l/h/m2 (P>0.25; ratio B/A 1.04). The corresponding harmonic mean half-life values were 10.1 and 8.5 h. The two treatment regimens had similar tolerability profiles; the median absolute neutrophil count nadirs were 681/mm3 during treatment with docetaxel alone and 975/mm3 during aprepitant coadministration.Conclusions Aprepitant had no clinically significant effect on either the pharmacokinetics or toxicity of standard doses of docetaxel in cancer patients. Aprepitant at clinically recommended doses may have a low potential to affect the pharmacokinetics of intravenous chemotherapeutic agents metabolized by CYP3A4. 相似文献
62.
Smith RA Cokkinides V Brooks D Saslow D Shah M Brawley OW 《CA: a cancer journal for clinicians》2011,61(1):8-30
Each year the American Cancer Society (ACS) publishes a summary of its recommendations for early cancer detection, a report on data and trends in cancer screening rates, and select issues related to cancer screening. This article summarizes the current ACS guidelines, describes the anticipated impact of new health care reform legislation on cancer screening, and discusses recent public debates over the comparative effectiveness of different colorectal cancer screening tests. The latest data on the utilization of cancer screening from the National Health Interview Survey is described, as well as several recent reports on the role of health care professionals in adult utilization of cancer screening. 相似文献
63.
Davis AJ Gelmon KA Siu LL Moore MJ Britten CD Mistry N Klamut H D'Aloisio S MacLean M Wainman N Ayers D Firby P Besterman JM Reid GK Eisenhauer EA 《Investigational new drugs》2003,21(1):85-97
Purpose: MG98 is a second generation phosphorothioate antisense oligodeoxynucleotide which is a highly specific inhibitor of translation of the mRNA for human DNA MeTase I (DNMT 1). This phase I study examined the toxicity and pharmacologic profile of MG98 administered as a continuous 21-day intravenous infusion every 4 weeks. Patients and methods: Fourteen patients with solid cancers received a total of 25 cycles of MG98 at doses ranging from 40 to 240 mg/m2/day. Steady-state concentrations of MG98 were measured as were several pharmacodynamic assessments including mRNA of the target gene, DNMT1, in PBMC. In addition, other potential surrogate markers of drug effects were explored, including hemoglobin F, Vimentin and GADD45. Results: Dose limiting effects were drug-related reversible transaminase elevation and fatigue seen at doses of 240, 200 and 160 mg/m2/day. The dose level of 80 mg/m2/day was felt to be safe and tolerable when delivered on this schedule. No evidence of antitumor activity was observed. Although pharmacokinetic analysis revealed that at the higher dose levels, mean Css values of MG98 were approximately 10-fold times the IC50 values associated with target inhibition in vitro, the extent of MG98 penetration into target tumors in this trial was not determined. No consistent, dose-related changes in correlative markers including DNMT1 mRNA, hemoglobin F, Vimentin and GADD45, were observed. Conclusions: This schedule of MG98 given as a 21-day continuous intravenous infusion every 4 weeks was poorly tolerated in the highest doses; therefore, further disease-site specific evaluation of the efficacy of this agent will utilize a more favorable, intermittent dosing schedule. Pharmacodynamic evaluations undertaken in an attempt to explore and validate the biological mechanisms of MG98 did not show dose-related effects. 相似文献
64.
Michelle Harvie Mary Pegington Sacha J. Howell Nigel Bundred Phil Foden Judith Adams Lee Graves Alastair Greystoke Mark P. Mattson Roy G. Cutler Julie Williamson Karen Livingstone Debbie McMullen Katharine Sellers Cheryl Lombardelli Grace Cooper Sarah McDiarmid Anthony Howell 《British journal of cancer》2022,126(8):1157
Background Excess adiposity at diagnosis and weight gain during chemotherapy is associated with tumour recurrence and chemotherapy toxicity. We assessed the efficacy of intermittent energy restriction (IER) vs continuous energy restriction (CER) for weight control and toxicity reduction during chemotherapy.Methods One hundred and seventy-two women were randomised to follow IER or CER throughout adjuvant/neoadjuvant chemotherapy. Primary endpoints were weight and body fat change. Secondary endpoints included chemotherapy toxicity, cardiovascular risk markers, and correlative markers of metabolism, inflammation and oxidative stress.Results Primary analyses showed non-significant reductions in weight (−1.1 (−2.4 to +0.2) kg, p = 0.11) and body fat (−1.0 (−2.1 to +0.1) kg, p = 0.086) in IER compared with CER. Predefined secondary analyses adjusted for body water showed significantly greater reductions in weight (−1.4 (−2.5 to −0.2) kg, p = 0.024) and body fat (−1.1 (−2.1 to −0.2) kg, p = 0.046) in IER compared with CER. Incidence of grade 3/4 toxicities were comparable overall (IER 31.0 vs CER 36.5%, p = 0.45) with a trend to fewer grade 3/4 toxicities with IER (18%) vs CER (31%) during cycles 4–6 of primarily taxane therapy (p = 0.063).Conclusions IER is feasible during chemotherapy. The potential efficacy for weight control and reducing toxicity needs to be tested in future larger trials.Clinical trial registration ISRCTN04156504.Subject terms: Randomized controlled trials, Breast cancer, Nutrition, Weight management, Breast cancer 相似文献
65.
66.
67.
Bradshaw T Wearden A Marshall M Warburton J Husain N Pedley R Escott D Swarbrick C Lovell K 《International journal of nursing studies》2012,49(4):398-406
BackgroundYoung people with early psychosis often gain a significant amount of weight after the initiation of anti-psychotic treatment. Despite the current policy guidance to develop and evaluate ‘healthy living’ interventions for people with psychosis there remains a paucity of research. Our aim was to develop an acceptable, feasible, culturally sensitive and potentially effective ‘healthy living’ intervention, specifically for young people with early psychosis.MethodsUsing the Medical Research Council guidelines for developing and evaluating complex interventions we conducted a number of studies to devise a ‘healthy living’ intervention. We used a ‘top down’ (published evidence), bottom up (stakeholder perspectives) approach, which included updating a systematic review, identifying a theoretical basis for the intervention, exploring the perspectives of service users and health professionals, and identifying key cultural issues. The results of these studies were synthesised to determine the content and delivery of the intervention.ResultsThe intervention developed comprised eight individual sessions to be delivered by a support time recovery worker over a 12 month period with emphasis on individualised action plans to facilitate participatory exercise and changes in diet. To optimise engagement, choice and self management a booklet and website were developed to provide participants with educational advice, healthy eating recipes and other materials.ConclusionUsing the Medical Research Council guidelines we have developed a potentially effective, feasible and acceptable ‘healthy living’ intervention for people with psychosis using early intervention services in the UK. 相似文献
68.
The association between smoking and HIV disease progression has been examined in several studies; however, findings have been inconsistent. We examined the effect of recent cigarette smoking on CD4(+) T cell count/μl (CD4 count) and HIV RNA concentration (HIV viral load (VL)) among two HIV-infected cohorts with alcohol problems in Massachusetts in the periods 1997-2001 and 2001-2006 using a prospective cohort design and linear mixed models. Smoking groups were defined as: minimal or non-smokers, light smokers, moderate smokers, and heavy smokers. Age, alcohol use, injection drug use, depressive symptoms, gender, annual income, and antiretroviral therapy adherence were considered as potential confounders. Among 462 subjects, no significant differences in CD4 count or VL were found between smoking groups. Using minimal or non-smokers as the reference group, the adjusted mean differences in CD4 count were: 8.2 (95% confidence interval (CI): -17.4, 33.8) for heavy smokers; -0.1 (95% CI: -25.4, 5.1) for moderate smokers; and -2.6 (95% CI: -28.3, 3.0) for light smokers. For log10 VL, the adjusted differences were: 0.03 (95% CI: -0.12, 0.17) for heavy smokers; -0.06 (95% CI: -0.20, 0.08) for moderate smokers; and 0.14 (95% CI -0.01, 0.28) for light smokers. This study did not find an association between smoking cigarettes and HIV disease progression as measured by CD4 cell count and VL. 相似文献
69.
High responsiveness of HLA-B57-restricted Gag-specific CD8+ T cells in vitro may contribute to the protective effect of HLA-B57 in HIV-infection 总被引:1,自引:0,他引:1
Jansen CA Kostense S Vandenberghe K Nanlohy NM De Cuyper IM Piriou E Manting EH Miedema F van Baarle D 《European journal of immunology》2005,35(1):150-158
HLA-B57 has been shown to be associated with long-term asymptomatic HIV-1 infection. To investigate the biological mechanism by which the HLA-B57 allele could protect from HIV-1 disease, we studied both the number of CD8(+) T cells as well as CD8(+) T cell responsiveness directed to different HIV-1 Gag peptides presented by HLA-A2, -B8 or -B57. T cells specific for the HLA-B57 peptide KAFSPEVIPMF responded more readily and to a higher extend to antigenic stimulation in vitro than T cells specific for the HLA-A2 peptide SLYNTVATL or the HLA-B8 peptide EIYKRWII. This phenomenon was reproducible with T cells from individuals expressing HLA-B57 in combination with one or both of the other alleles and was persistent during long-term follow-up. Lower reactivity of A2- and B8-restricted T cells was not explained by mutations in the B8- or A2-restricted Gag-peptides. Moreover, no correlation between peptide mutation frequency and IFN-gamma production by the corresponding Gag-specific T cells was observed. In conclusion, functional differences were observed between T cells specific for HIV epitopes derived from the same protein presented by different HLA molecules. B57-restricted KAFSPEVIPMF-specific CD8(+) T cells have relatively high responsiveness, which could contribute to the protective effect of HLA-B57 in HIV infection. 相似文献
70.
Debbie Zittema Else van den Berg Esther Meijer Wendy E. Boertien Anneke C. Muller Kobold Casper F.M. Franssen Paul E. de Jong Stephan J.L. Bakker Gerjan Navis Ron T. Gansevoort 《Clinical journal of the American Society of Nephrology》2014,9(9):1553-1562