全文获取类型
收费全文 | 6241篇 |
免费 | 339篇 |
国内免费 | 14篇 |
专业分类
耳鼻咽喉 | 50篇 |
儿科学 | 221篇 |
妇产科学 | 100篇 |
基础医学 | 757篇 |
口腔科学 | 147篇 |
临床医学 | 509篇 |
内科学 | 1103篇 |
皮肤病学 | 83篇 |
神经病学 | 419篇 |
特种医学 | 224篇 |
外科学 | 739篇 |
综合类 | 86篇 |
一般理论 | 5篇 |
预防医学 | 281篇 |
眼科学 | 207篇 |
药学 | 768篇 |
1篇 | |
中国医学 | 80篇 |
肿瘤学 | 814篇 |
出版年
2023年 | 36篇 |
2022年 | 127篇 |
2021年 | 213篇 |
2020年 | 113篇 |
2019年 | 149篇 |
2018年 | 185篇 |
2017年 | 115篇 |
2016年 | 159篇 |
2015年 | 208篇 |
2014年 | 245篇 |
2013年 | 333篇 |
2012年 | 536篇 |
2011年 | 501篇 |
2010年 | 263篇 |
2009年 | 265篇 |
2008年 | 387篇 |
2007年 | 382篇 |
2006年 | 368篇 |
2005年 | 351篇 |
2004年 | 307篇 |
2003年 | 264篇 |
2002年 | 223篇 |
2001年 | 82篇 |
2000年 | 81篇 |
1999年 | 76篇 |
1998年 | 47篇 |
1997年 | 26篇 |
1996年 | 37篇 |
1995年 | 39篇 |
1994年 | 31篇 |
1993年 | 34篇 |
1992年 | 47篇 |
1991年 | 44篇 |
1990年 | 34篇 |
1989年 | 31篇 |
1988年 | 20篇 |
1987年 | 18篇 |
1986年 | 14篇 |
1985年 | 20篇 |
1984年 | 26篇 |
1983年 | 17篇 |
1982年 | 11篇 |
1981年 | 12篇 |
1980年 | 18篇 |
1979年 | 10篇 |
1975年 | 9篇 |
1974年 | 8篇 |
1973年 | 6篇 |
1972年 | 6篇 |
1971年 | 6篇 |
排序方式: 共有6594条查询结果,搜索用时 15 毫秒
61.
62.
Giri TK de Frutos PG Yamazaki T Villoutreix BO Dahlbäck B 《Thrombosis and haemostasis》1999,82(6):1627-1633
The molecular consequences of two naturally occurring mutations in the thrombin-sensitive region of protein S were investigated using a combination of recombinant protein expression, functional analysis and molecular modelling. Both mutations (R49H and R70S) have been found in thrombosis patients diagnosed as having type I protein S deficiency. Molecular modelling analysis suggested the R49H substitution not to disrupt the structure of thrombin-sensitive region, whereas the R70S substitution could affect the 3D structure mildly. To elucidate the molecular consequences of these substitutions experimentally, site directed mutagenesis of protein S cDNA and expression in mammalian cells created the two mutants. The secretion profiles and functional anticoagulant activities of the protein S mutants were characterised. Secretion of the R49H mutant was similar to that of wild type protein S, whereas the R70S mutant showed moderately decreased expression. Neither of the mutants showed any major functional defects as cofactors to activated protein C (APC) in an APTT-based assay or in degradation of factor Va. However, both mutants demonstrated decreased activity in a factor VIIIa degradation assay, which in addition to APC and protein S also included factor V as synergistic APC cofactor. In conclusion, the R49H substitution did not produce a quantitative abnormality in vitro, raising doubts as to whether it caused the type I deficiency. In contrast, the experimental data obtained for the R70S mutant agrees well with the observed type I deficiency. Our study illustrates that in vitro experimental characterisation together with computer-based structural analysis are useful tools in the analysis of the relationship between naturally occurring mutations and clinical phenotypes. 相似文献
63.
A histopathologically proven case of cerebral toxoplasmosis in a young HIV positive patient has been presented. The clinical problems in management are highlighted. 相似文献
64.
AIM: In order to define their demographics and medical conditions, 218 diabetic patients undergoing hemodialysis in Brooklyn were interviewed and their charts reviewed. METHODS: Patient rehabilitation was assessed with the Karnofsky score, and the urea reduction rate as well as serum albumin and hematocrit levels evaluated adequacy of hemodialysis. RESULTS: The majority of patients (167) were African-American, 25 were Whites, 19 patients were Hispanic and 6 were Asian. One patient was a Native American. The mean age was 60.5 years (range 16-88), and the majority, 52%, were women. Rehabilitation was poor, the mean Karnofsky score being 65.1+/-20.8, and only 6% of patients were working. By linear regression, there was no difference in the Karnofsky score according to gender, age, race, type of diabetes, education, family income or hematocrit level. Only the patients' self-perception of their psyche function, or how well they thought they were doing, was significant. CONCLUSION: Further work is needed to examine the reasons for the poor rehabilitation of diabetics on dialysis in Brooklyn. 相似文献
65.
Steven R Alberts Mark Schroeder Charles Erlichman Preston D Steen Nathan R Foster Dennis F Moore Kendrith M Rowland Suresh Nair Loren K Tschetter Tom R Fitch 《Journal of clinical oncology》2004,22(24):4944-4950
PURPOSE: Gemcitabine remains the standard therapy for metastatic pancreatic adenocarcinoma (ACA), but has limited activity. ISIS-2503 is an antisense compound directed against H-ras with preclinical activity against pancreatic ACA in tumor models. The combination of ISIS-2503 and gemcitabine has been evaluated in a prior phase I study. METHODS: Patients with metastatic or locally advanced pancreatic ACA not amenable to surgery or local radiation received gemcitabine 1,000 mg/m(2) intravenously over 30 minutes on days 1 and 8 and ISIS-2503 6 mg/kg/d as a continuous intravenous infusion over 14 days of an every-3-weeks cycle. Responses were monitored by radiologic imaging every 6 weeks. RESULTS: Forty-eight eligible patients were enrolled, 43 with metastatic disease. Median follow-up was 12.6 months (range, 2.2 to 16.8 months) for living patients. A median of four cycles of treatment was given (range, 1 to 18 cycles). All patients were assessable for response and toxicity. The 6-month survival percentage was 57.5% (95% CI, 44.9% to 73.5%) and the median survival was 6.6 months. The response rate was 10.4% (one complete response, four partial responses). Clinically significant toxicity was limited except for one fatal pulmonary embolism. CONCLUSION: This study shows a promising response rate to the combination of gemcitabine and ISIS-2503 in patients with pancreatic ACA. The observed 6-month survival rate in these patients met our protocol-defined criteria for success. This regimen is tolerable, but is of unclear benefit. Additional studies evaluating the role of gemcitabine and ISIS-2503 in the treatment of pancreatic ACA should be considered. 相似文献
66.
The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis.
A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified
targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly
identified targets and their role in cancer. Emerging data also provide new clues towards a previously unappreciated link
between these various cellular processes. The present review attempts to provide a quick tutorial to the reader about the
evolving significance of p21-activated kinases and small GTPases in breast cancer, using information from mouse models, tissue
culture studies, and human materials. 相似文献
67.
Martin A. Graham Suresh Senan Hernani Robin Jr. Nils Eckhardt Dennis Lendrem Jeffery Hincks Dennis Greenslade Roy Rampling Stanley B. Kaye Reinhard von Roemeling Paul Workman 《Cancer chemotherapy and pharmacology》1997,40(1):1-10
Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-di-N-oxide; SR 259075) is a selective hypoxic cell cytotoxic agent that is bioreductively activated in tumours to a reactive-drug
free radical. Preclinically the agent has been shown to possess additive and synergistic anti-tumour activity in combination
with radiotherapy and chemotherapy regimens. In the present study the pharmacokinetics and metabolism of tirapazamine were
investigated in mice and patients as part of pre-clinical and phase I investigations. The objectives of this work were twofold;
firstly, to evaluate retrospectively the utility of a pharmacokinetically guided dose-escalation (PGDE) strategy for tirapazamine,
and secondly, to investigate if pharmacologically relevant plasma concentrations could be achieved at tolerable doses. Pharmacokinetic
studies for PGDE were conducted in mice at four dose levels ranging from one-tenth of the LD10 to the LD50. The AUC at the LD10 (2932 μg ml-1min) was used to determine a target AUC value of 1173 μg ml-1min (equivalent to 40% of the mouse LD10 AUC) for clinical studies. A phase I study to investigate the tolerance of a single i.v. infusion of tirapazamine (once every
3 weeks) was initiated with close pharmacokinetic monitoring. The starting dose (36 mg/m2) was based on toxicity data obtained in the mouse, rat and dog. Doses were escalated by increases in the volume and duration
of infusion. A retrospective analysis of the pharmacokinetic and toxicity data was then made to determine the utility of a
PGDE approach. The drug exhibited a steep dose-lethality relationship in mice (LD10 294 mg/m2, LD50 303 mg/m2). The major gross toxicities were body-weight loss (15–20%), pilo-erection and hypoactivity at all dose levels. Sporadic
ptosis and conjunctivitis were observed at doses of >300 mg/m2. The plasma elimination of tirapazamine fitted a monoexponential open model, with rapid elimination from the plasma (t
1/2=36±0.65 min) occuring at the LD10 dose of 294 mg/m2. A 10.3-fold increase in dose resulted in a 25.0-fold increase in AUC. Clinically, doses were escalated over the range of
36–450 mg/m2. Ototoxicity (tinnitus and reversible hearing loss) was dose-limiting at 450 mg/m2 and the MTD was 390 mg/m2 for this schedule. Pharmacokinetic analyses in patients revealed that the elimination of tirapazamine in patients was generally
bi-phasic, with low inter-patient variability being found in clearance. A 12.5-fold increase in dose resulted in a 19.0-fold
increase in AUC. There was good quantitative agreement in metabolite formation between mice and humans with respect to the
two- and four-electron bioreductive metabolites. AUC values recorded for tirapazamine at the MTD of 390 mg/m2 (range 1035–1611 μg ml-1min) were similar to the target AUC in mice. Importantly, these levels are consistent with the levels required for radiation-dose
enhancement and effective combination with cisplatin in mice. Given (a) the similarities in plasma pharmacokinetics and metabolism
observed at the target AUC/MTD in mice, rats, dogs and humans, (b) the similar degree of plasma protein binding seen between
species and (c) the relatively low inter-patient variability noted in drug clearance, a successful PGDE approach should have
been feasible. The results also indicate that potentially therapeutic levels of tirapazamine are achievable in patients at
tolerable doses.
Received: 27 May 1996 / Accepted: 30 September 1996 相似文献
68.
M. S. Vidyasagar Suresh Rao Donald J. Fernandes Ramanujam A. S. 《Indian journal of otolaryngology and head and neck surgery》1998,50(1):69-72
Primary Ewing’s sarcoma of the nasal bone has not been previously described. This case presented as a mass in the left ala
of the nose in a five year old female child. The clinical, radiological, microscopic features are described and a review of
literature is presented. The case was treated with neoadjuvant chemotherapy and local electron beam radiation therapy. The
child was free of disease when she reported for follow up in July 1997. Although wide excision is part of the treatment approach
in Ewing’s sarcoma, in sites where surgery is not suitable local radiotherapy and chemotherapy adequately controls primary
disease. 相似文献
69.
M. S. Vidyasagar Suresh Rao Donald J. Fernandes A. S. Ramanujam 《Indian journal of otolaryngology and head and neck surgery》1998,50(1):69-72
Primary Ewing’s sarcoma of the nasal bone has not been previously described. This case presented as a mass in the left ala of the nose in a five year old female child. The clinical, radiological, microscopic features are described and a review of literature is presented. The case was treated with neoadjuvant chemotherapy and local electron beam radiation therapy. The child was free of disease when she reported for follow up in July 1997. Although wide excision is part of the treatment approach in Ewing’s sarcoma, in sites where surgery is not suitable local radiotherapy and chemotherapy adequately controls primary disease. 相似文献
70.