全文获取类型
收费全文 | 886篇 |
免费 | 117篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 17篇 |
儿科学 | 14篇 |
妇产科学 | 35篇 |
基础医学 | 67篇 |
口腔科学 | 14篇 |
临床医学 | 67篇 |
内科学 | 204篇 |
皮肤病学 | 39篇 |
神经病学 | 22篇 |
特种医学 | 23篇 |
外科学 | 132篇 |
综合类 | 22篇 |
预防医学 | 52篇 |
眼科学 | 3篇 |
药学 | 71篇 |
肿瘤学 | 222篇 |
出版年
2022年 | 10篇 |
2021年 | 8篇 |
2020年 | 10篇 |
2019年 | 16篇 |
2018年 | 20篇 |
2017年 | 11篇 |
2016年 | 25篇 |
2015年 | 21篇 |
2014年 | 24篇 |
2013年 | 33篇 |
2012年 | 65篇 |
2011年 | 56篇 |
2010年 | 24篇 |
2009年 | 24篇 |
2008年 | 49篇 |
2007年 | 48篇 |
2006年 | 37篇 |
2005年 | 40篇 |
2004年 | 43篇 |
2003年 | 36篇 |
2002年 | 30篇 |
2001年 | 20篇 |
2000年 | 29篇 |
1999年 | 21篇 |
1998年 | 10篇 |
1997年 | 11篇 |
1996年 | 5篇 |
1995年 | 9篇 |
1994年 | 9篇 |
1993年 | 9篇 |
1992年 | 14篇 |
1991年 | 16篇 |
1990年 | 17篇 |
1989年 | 15篇 |
1988年 | 16篇 |
1987年 | 17篇 |
1986年 | 19篇 |
1985年 | 18篇 |
1984年 | 5篇 |
1983年 | 8篇 |
1982年 | 10篇 |
1981年 | 10篇 |
1980年 | 10篇 |
1979年 | 13篇 |
1978年 | 12篇 |
1977年 | 12篇 |
1975年 | 5篇 |
1974年 | 9篇 |
1968年 | 5篇 |
1963年 | 3篇 |
排序方式: 共有1004条查询结果,搜索用时 31 毫秒
11.
S C Hadler D P Francis J E Maynard S E Thompson F N Judson D F Echenberg D G Ostrow P M O'Malley K A Penley N L Altman 《The New England journal of medicine》1986,315(4):209-214
To study the duration of antibody persistence and protection provided by the hepatitis B vaccine, we followed 773 homosexual men for five years after completion of vaccination. Among the 635 participants in whom antibody levels above 9.9 sample ratio units (SRU) developed after vaccination, 15 percent lost antibody altogether, and in another 27 percent, antibody levels declined below 10 SRU within five years. The extent of the maximal antibody response strongly predicted the persistence of protective antibody. Hepatitis B infection occurred in 55 men; 8 of these infections were clinically important (characterized by the presence of the hepatitis B surface antigen and elevation of liver-enzyme levels), and two of the patients became hepatitis B virus carriers. The long-term risk of hepatitis B infection was inversely related to the maximal antibody response to vaccine. Most severe infections occurred among those who responded poorly or had no response to the vaccination. The risk of late infection with hepatitis B in those with an initially adequate vaccine response increased markedly when antibody levels decreased below 10 SRU, but only 1 of 34 late infections resulted in viremia and liver inflammation. A second series of vaccinations induced a moderate antibody response in 50 percent of the subjects who initially had no response or a poor response; however, the persistence of antibody was poor. Both antibody loss and the risk of severe disease should be considered when booster-dose strategies for the hepatitis B vaccine are being designed. 相似文献
12.
Recruitment and baseline epidemiologic profile of participants in the first phase 3 HIV vaccine efficacy trial 总被引:2,自引:0,他引:2
Harro CD Judson FN Gorse GJ Mayer KH Kostman JR Brown SJ Koblin B Marmor M Bartholow BN Popovic V;VAX Study Group 《Journal of acquired immune deficiency syndromes (1999)》2004,37(3):1385-1392
OBJECTIVE: To describe recruitment and baseline epidemiologic characteristics of volunteers in the first phase 3 placebo-controlled trial of a recombinant gp120 HIV vaccine (AIDSVAX B/B). METHODS: Volunteers were gay/bisexual men or women at risk for sexually transmitted HIV infection. Recruitment strategies, demographics, and risk factors were assessed. HIV status was determined by standard HIV-1 antibody assays. Seronegative/viremic HIV infection at enrollment was determined using the HIV-1 nucleic acid test. RESULTS: From June 1998 through October 1999, 5417 of 7185 volunteers screened were enrolled at 61 sites in the United States, Canada, and The Netherlands. Successful recruitment methods included distribution of study information at gay venues, advertising and media coverage, and referrals from volunteers. Most volunteers were altruistically motivated, men (98%), young (median, 36 years), white (83%), well educated (61% college education or more), and at high risk for HIV during the 6 months before enrollment. At baseline, 14 were HIV infected (12 were seronegative but viremic; 2 were seropositive and viremic). CONCLUSION: Men and women at high risk for sexually transmitted HIV infection were successfully recruited for the first phase 3 HIV vaccine efficacy trial. Knowledge of recruitment and baseline epidemiologic characteristics of participants in this trial will provide valuable guidance for designing and conducting future trials. 相似文献
13.
Yamada Y Kubota T Hoshiya Y Asanuma F Koh J Kitajima M Coley H Judson I 《Oncology reports》1996,3(4):613-617
The antitumor effect of N-2, N-4, N-6-trihydroxymethyl-N-2, N-4, N-6-trimethylmelamine (trimelamol), a synthetic analogue of hexamethylmelamine, was investigated using human breast carcinoma xenografts in nude mice. Four tumor models, T-61, Br-10, R-27 and MCF-7 were estrogen receptor (ER)-positive and their growth was estradiol-dependent. The MX-1 model was ER-negative and grew estradiol-independently. Sixty mg of trimelamol per kg dissolved in 5% dimethylsulphoxide (DMSO) with 5% glucose was administered intraperitoneally for 5 days weekly for three weeks. Trimelamol showed potent antitumor activity on T-61 and MX-1 in a dose-responsive manner with a marginal effect on Br-10, whilst R-27 and MCF-7 were insensitive to this agent. This antitumor spectrum on human breast carcinoma xenografts was similar to that of hexamethylmelamine previously reported using the same xenograft models. Trimelamol is water-soluble and does not require metabolic activation which is needed for hexamethylmelamine. These advantages allow the paraenteral administration of trimelamol, and warrant the further investigation of this drug for breast carcinomas. 相似文献
14.
Beatrice M Seddon Geoffrey S Payne Laura Simmons Ruth Ruddle Rachel Grimshaw Siew Tan Alison Turner Florence Raynaud Gavin Halbert Martin O Leach Ian Judson Paul Workman 《Clinical cancer research》2003,9(14):5101-5112
PURPOSE: To perform a Phase I study of SR-4554, a fluorinated 2-nitroimidazole noninvasive probe of tumor hypoxia detected by (19)F magnetic resonance spectroscopy (MRS). EXPERIMENTAL DESIGN: SR-4554 administration, on days 1 and 8, was followed by plasma sampling for pharmacokinetic studies and by three MRS studies performed over 24 h on days 8 and 9. Unlocalized MR spectra were acquired from tumor (10- or 16-cm dual resonant 1H/19F surface coil; 1.5 T Siemens Vision MR system; 2048 transients acquired over 34 min; 1.28-ms adiabatic pulse; repetition time, 1 s). Plasma drug concentrations were measured with a validated high-performance liquid chromatography method. Noncompartmental pharmacokinetic analysis was performed. RESULTS: Eight patients underwent pharmacokinetic studies, receiving doses of SR-4554 of 400-1600 mg/m(2). Peak plasma concentrations increased linearly with the SR-4554 dose (r(2) = 0.80; P = 0.0002). The plasma elimination half-life was relatively short (mean +/- SD, 3.28 +/- 0.59 h), and plasma clearance was quite rapid (mean +/- SD, 12.8 +/- 3.3 liters/h). Urinary recovery was generally high. SR-4554 was well tolerated. A single patient experienced dose-limiting toxicity (nausea and vomiting) at 1600 mg/m(2). The maximum tolerated dose was 1400 mg/m(2). SR-4554 was detected spectroscopically in tumors immediately after infusion at doses of 400-1600 mg/m(2). At the highest dose (1600 mg/m(2)), SR-4554 was detectable in tumor at 8 h, but not at 27 h. CONCLUSIONS: SR-4554 has plasma pharmacokinetic and toxicity profiles suitable for use as a hypoxia probe. It can be detected in tumors by unlocalized MRS. Additional clinical studies are warranted. 相似文献
15.
Dr Ole S. Nielsen Jean-Yves Blay Ian R. Judson Martine van Glabbeke Jaap Verweij Allan T. van Oosterom 《American Journal of Cancer》2003,2(3):211-221
In the present paper the treatment of advanced and metastatic soft tissue sarcoma is reviewed with the primary emphasis on chemotherapy. One of the major advances in the treatment of soft tissue sarcomas is their treatment by multidisciplinary teams in specialized centers. Despite optimal local treatment of the primary tumor, disseminated disease will develop in many patients. Consequently, chemotherapy has been extensively studied but, unfortunately, the responsiveness of these tumors to chemotherapy has been disappointingly low. Doxorubicin and ifosfamide appear to be the most effective drugs — the latter with a somewhat higher toxicity at effective dosages. Other drugs with some first line activity are dacarbazine, liposomal doxorubicin and possibly trabectedin (ET-743). Imatinib is very effective in gastrointestinal stromal tumors (GIST) where it is now the treatment of choice. The combination of doxorubicin and ifosfamide increases the response rate without affecting overall survival. For these reasons, single agent doxorubicin is, in many centers, considered the standard treatment for advanced soft tissue sarcoma, and combination chemotherapy should be reserved for special subgroups of patients such as young patients with chemosensitive tumors. Chemotherapy for patients with advanced and metastatic soft tissue sarcoma is inadequate at present and new drugs are desperately needed. Fortunately, exciting new drugs are under development and hopefully they will improve the treatment of patients with this disease. 相似文献
16.
Ruth Plummer Charlotte Rees Andrew Hughes Philip Beale Martin Highley Jose Trigo Sathyarathnarn Gokul Ian Judson Hilary Calvert Ann Jackman Fraser Mitchell Robert Smith Edwin Douglass 《Clinical cancer research》2003,9(4):1313-1322
PURPOSE: ZD9331 is a novel, direct-acting antifolate cytotoxic that does not require polyglutamation for activity, and is a specific thymidylate synthase inhibitor. This Phase I trial aimed to determine the maximum tolerated dose of ZD9331, given as a 30-min i.v. infusion on days 1 and 8 of a 21-day cycle. Pharmacokinetic parameters and tumor response were also assessed. EXPERIMENTAL DESIGN: A total of 71 patients, with a range of solid malignancies and refractory to standard therapies (44% had received > or =3 prior chemotherapy regimens), were treated. The most common malignancies were colorectal cancer (35% of patients) and ovarian cancer (31%). ZD9331 was escalated from 4.8 mg/m(2)/day. RESULTS: Dose-limiting toxicity occurred at 162.5 mg/m(2) ZD9331, with grade 4 thrombocytopenia, grade 4 neutropenia lasting > or =7 days, and grade 3 nonhematologic toxicity. Plasma clearance of ZD9331 was slow and dose-dependent; however, ZD9331 pharmacokinetics were nonlinear. Pharmacodynamics of ZD9331 were determined by measurement of plasma deoxyuridine, which increased at all of the dose levels; dose-related increases in plasma deoxyuridine were significant (P = 0.003) on day 5. Stable disease was observed in 37% of patients; 23% of ovarian cancer patients had a > or =50% reduction in CA125 levels. CONCLUSIONS: The maximum tolerated dose of this schedule was 130 mg/m(2). The toxicity profile at this dose was acceptable, with 7 of 28 patients treated developing grade 3/4 neutropenia and thrombocytopenia, 2 grade 4 diarrhea, and 2 grade 3/4 rash. This schedule was convenient and demonstrated activity in extensively pretreated patients; therefore, this is the recommended dose for study in Phase II trials. 相似文献
17.
Adams CD Januszkiewcz JS Judson J 《The Australian and New Zealand journal of surgery》2000,70(6):401-404
BACKGROUND: This study was performed to review the changing pattern of incidence of severe craniomaxillofacial (CMF) trauma in Auckland over 8 years (1989-1997) and to audit the involvement of the regional plastic surgery service. METHODS: A review of prospectively collected admission data of patients admitted to the Auckland Hospital Department of Critical Care Medicine (DCCM) with severe CMF trauma during 1997. A comparison is made with similar data from 1989. Injury severity was defined using the Injury Severity Score (ISS). RESULTS: Twenty-six patients with severe CMF trauma were admitted to Auckland Hospital DCCM in 1997. Their average ISS was 35. Eighty per cent had a significant head injury. Sixty-two per cent had injuries due to road traffic accidents (RTA) and 42% had positive blood alcohol levels, including 37% of the RTA victims. Twenty-three per cent had their surgical care provided by the regional plastic surgery service. In 1989, 55 patients were admitted to DCCM with severe CMF trauma. The average ISS was 36. Ninety-five per cent had a significant head injury. Seventy-three per cent had injuries due to RTA and 55% had positive blood alcohol, including 60% of the RTA group. CONCLUSIONS: Patients with severe CMF trauma make up a significant proportion of trauma admissions to DCCM and have a high incidence of life-threatening injuries. A multidisciplinary approach is essential. The nature and severity of these injuries has not changed over the last decade. There has been a clear decrease in the incidence of these injuries. This seems to be due to a profound decrease in the rate of RTA associated with alcohol intoxication. 相似文献
18.
Prognostic factors in advanced synovial sarcoma: an analysis of 104 patients treated at the Royal Marsden Hospital. 总被引:4,自引:0,他引:4
AIMS: Key prognostic factors at diagnosis of synovial sarcoma are well defined from the literature. There are few data regarding prognostic parameters in the setting of advanced disease. Our aim was to look specifically at a cohort of patients with advanced synovial sarcoma and to identify potential prognostic factors. PATIENTS AND METHODS: One hundred and four patients with advanced synovial sarcoma were identified from the Royal Marsden Hospital's sarcoma database between 1978 and 2003. Patient data were analysed retrospectively. Most patients were aged between 20 and 50 years at diagnosis. Seventy-one patients were deceased at the time of analysis. Ninety-two patients received chemotherapy for management of advanced disease (most commonly doxorubicin + ifosfamide). RESULTS: Median survival following development of advanced disease was 22 months. Predictors of survival with advanced disease were age <35 years (P = 0.03) and response to first-line chemotherapy (P = 0.05). The response rate to doxorubicin plus ifosfamide was 58.6%, and this was superior to either agent when given singly. Metastasectomy was not associated with improved prognosis in this series. CONCLUSIONS: Synovial sarcoma is a chemosensitive soft tissue sarcoma. Compared with historical controls, survival with advanced disease seems to have improved over the years, possibly as a result of better use of chemotherapy. Age <35 years and response to first-line chemotherapy predict for improved survival with advanced disease. 相似文献
19.
Craig Gerrand Nick Athanasou Bernadette Brennan Robert Grimer Ian Judson Bruce Morland David Peake Beatrice Seddon Jeremy Whelan On behalf of the British Sarcoma Group 《Clinical sarcoma research》2016,6(1):7
This document is an update of the British Sarcoma Group guidelines published in 2010. The aim is to provide a reference standard for the clinical care of patients in the UK with bone sarcomas. Recent recommendations by the European Society of Medical Oncology, The National Comprehensive Cancer Network and The National Institute for Health and Care Excellence have been incorporated, and the literature since 2010 reviewed. The standards represent a consensus amongst British Sarcoma Group members in 2015. It is acknowledged that these guidelines will need further updates as care evolves. The key recommendations are that bone pain or a palpable mass should always lead to further investigation and that patients with clinico-radiological findings suggestive of a primary bone tumour at any site in the skeleton should be referred to a specialist centre and managed by a fully accredited bone sarcoma multidisciplinary team. Treatment recommendations are provided for the major tumour types and for localised, metastatic and recurrent disease. Follow up schedules are suggested. 相似文献
20.
Imatinib mesylate is considered the standard first-line systemic treatment for patients with chronic myeloid leukaemia (CML)
and gastrointestinal stromal tumour (GIST) by targeting BCR-ABL and c-KIT tyrosine kinases, respectively. Indeed, imatinib
has substantially changed the clinical management and improved the prognosis of both diseases. Treatment with imatinib is
generally well tolerated, and the risk for severe adverse effects is low, generally occurring during the early phase of treatment
and correlating with imatinib dose, phase of disease and patient’s characteristics. This article summarises recent data on
safety profile of imatinib for the treatment of CML and GIST, including long-term side effects. Prolonged treatment with imatinib
in both diseases demonstrates excellent tolerability. There are few significant concerns and those that have emerged, like
cardiotoxicity, have far turned out to be exaggerated. 相似文献