全文获取类型
收费全文 | 3342篇 |
免费 | 248篇 |
国内免费 | 15篇 |
专业分类
耳鼻咽喉 | 43篇 |
儿科学 | 45篇 |
妇产科学 | 88篇 |
基础医学 | 472篇 |
口腔科学 | 51篇 |
临床医学 | 303篇 |
内科学 | 643篇 |
皮肤病学 | 82篇 |
神经病学 | 214篇 |
特种医学 | 162篇 |
外科学 | 607篇 |
综合类 | 40篇 |
一般理论 | 2篇 |
预防医学 | 218篇 |
眼科学 | 108篇 |
药学 | 218篇 |
中国医学 | 10篇 |
肿瘤学 | 299篇 |
出版年
2024年 | 5篇 |
2023年 | 26篇 |
2022年 | 23篇 |
2021年 | 108篇 |
2020年 | 77篇 |
2019年 | 118篇 |
2018年 | 125篇 |
2017年 | 78篇 |
2016年 | 74篇 |
2015年 | 122篇 |
2014年 | 137篇 |
2013年 | 205篇 |
2012年 | 262篇 |
2011年 | 273篇 |
2010年 | 190篇 |
2009年 | 148篇 |
2008年 | 212篇 |
2007年 | 202篇 |
2006年 | 211篇 |
2005年 | 195篇 |
2004年 | 208篇 |
2003年 | 166篇 |
2002年 | 132篇 |
2001年 | 24篇 |
2000年 | 28篇 |
1999年 | 32篇 |
1998年 | 26篇 |
1997年 | 19篇 |
1996年 | 15篇 |
1995年 | 23篇 |
1994年 | 16篇 |
1993年 | 17篇 |
1992年 | 6篇 |
1991年 | 14篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 10篇 |
1984年 | 11篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1978年 | 3篇 |
1965年 | 2篇 |
1964年 | 3篇 |
1961年 | 2篇 |
1960年 | 2篇 |
排序方式: 共有3605条查询结果,搜索用时 17 毫秒
41.
Purpose. The oxidative metabolism of metoprolol was investigated in two human lymphoblastoma cell-lines transfected with variants of cDNA for cytochrome P4502D6.
Methods. The regioselective and enantioselective features of the oxidations of deuterium-labeled pseudoracemic metoprolol were characterized by GC/MS analysis of the substrate and products.
Results. There were significant differences between the two P4502D6 variants in the formation kinetics of O-demethylmetoprolol and -hydroxymetoprolol. The h2D6-Val microsomes highly favored the formation of the O-demethylmetoprolol regioisomer 6.3:1 and 2.8:1, respectively from (R)-metoprolol-d0 and (S)-metoprolol-d2, while the corresponding ratios for h2D6v2 microsomes were much lower. For both variants, O-demethylmetoprolol formation favored the (R)-substrate 1.5 to 2-fold, while -hydroxymetoprolol formation was non-enantioselective. Similar Km values of metoprolol oxidation, 10-20 µM, were observed for the two microsomal preparations.
Conclusions. The regioselectivity, enantioselectivity, and Km values for the h2D6-Val microsomes resemble those observed for the native P4502D6 in human liver microsomes, whereas the h2D6v2 microsomes deviated remarkably in regioselectivity. 相似文献
42.
Danny D. Shen James P. Hosler Richard L. Schroder Daniel L. Azarnoff 《Journal of pharmacokinetics and pharmacodynamics》1980,8(1):53-68
The pharmacokinetics of hydralazine (H) and its acid-labile hydrazone metabolites were compared in rapid and slow acetylators. Following a 20-mg intravenous infusion, the elimination half-life (t1/2) and the apparent volume of distribution of H did not differ between the two groups. Plasma clearance estimates approached hepatic blood flow. When a single 100-mg dose of H was given-orally, the area under the plasma concentration-time curve (AUC) and systemic availability () in slow acetylators were, on the average, twice as high as in the rapid acetylators, indicating a difference in the extent of first-pass metabolism of the drug. Furthermore, the observed in the slow individuals exceeded theoretical predictions. Hence saturation of first-pass metabolism of H is suggested, and a nonlinear relationship between AUC and oral dose of H was indeed observed in the three subjects studied with two doses. The half-life of decline of the acidlabile metabolites was similar to the t1/2 of H. The AUCs for metabolites were 4–12 times larger than for the parentdrug. However, the ratio between the metabolite AUC and drug AUC did not differ irrespective ofroutes of administration or the acetylator status.This study was supported in part by Grant RR 828 from United States Public Health Service and a Research Starter grant from the Pharmaceutical Manufacturers Association Foundation, Inc. (D. D. S.). 相似文献
43.
Christian De Muynck Claude Cuvelier Danny Van Steenkiste Luc Bonnarens Jean Paul Remon 《Pharmaceutical research》1991,8(7):945-950
The effect of suppository bases on rabbit rectal mucosa was investigated using six triglyceride bases, polyethylene glycol, and a triglyceride base combined with monoglycerides or fatty acids and methyl esters of those acids. Rectal irritation was evaluated and scored according to defined pathological features. Pure triglycerides and a triglyceride to which a nonionic surfactant was added caused severe mucosal damage with ulceration and inflammation. Hyperemia was characteristic for irritation by polyethylene glycol suppositories. Mucosal damage by a pure triglyceride combined with monoglycerides or fatty acids and methyl esters of those acids was similar but statistically less pronounced than with all other bases. 相似文献
44.
Radical Resection of Periampullary Tumors in the Elderly: Evaluation of Long-term Results 总被引:5,自引:0,他引:5
Bathe OF Levi D Caldera H Franceschi D Raez L Patel A Raub WA Benedetto P Reddy R Hutson D Sleeman D Livingstone AS Levi JU 《World journal of surgery》2000,24(3):353-358
Increasingly, patients of advanced age are coming for evaluation of periampullary tumors. Although several studies have demonstrated
the safety of resecting periampullary tumors in older patients, few long-term survival data have been reported. Between 1983
and 1992 various periampullary masses were resected in 70 patients over age 65 (range 65–87 years). Total pancreatectomy was
performed in 11 patients, and 59 patients underwent pancreaticoduodenectomy. The mean duration of hospitalization was 17 ±
15 days. Major complications occurred in 27 patients (39%), and operative mortality rate was 8.5%. Overall median survival
was 24 months; and 5-year survival was 25%. Perioperative outcome was compared in patients aged 65 to 74 years and in patients
≥75 years old. The older age group required longer periods in the surgical intensive care unit postoperatively, but the long-term
survival was similar in the two age groups. Radical resection with the intent to cure periampullary tumors is safe in selected
patients of advanced age, and long-term survival is in the range of expected survival for younger patients with the same tumors. 相似文献
45.
性病艾滋病恐惧症110例心理咨询情况 总被引:2,自引:0,他引:2
目的:了解性病艾滋病恐惧症形成原因,寻找预防控制的措施.方法:对110例性病艾滋病恐惧症患者的临床症状和全身不适进行分析.结果:绝大多数患者都有不洁性交史,占82%,发病与患者的文化程度、心理因素和医学误导有关.结论:目前应加强对性病艾滋病恐惧症的预防、加强对性病艾滋病知识的宣传教育和心理疏导. 相似文献
46.
Danny Rischin Lester Peters Richard Fisher Andrew Macann Jim Denham Michael Poulsen Michael Jackson Lizbeth Kenny Michael Penniment June Corry David Lamb Bev McClure 《Journal of clinical oncology》2005,23(1):79-87
PURPOSE: To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial. PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost). RESULTS: Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79%; P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms. CONCLUSION: Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial. 相似文献
47.
June Corry Lester J Peters Ieta D' Costa Alvin D Milner Helen Fawns Danny Rischin Sandro Porceddu 《Radiotherapy and oncology》2005,77(2):137-142
BACKGROUND AND PURPOSE: The primary objective of this study was to estimate the rate of tumour response to a cyclical hypofractionated palliative radiotherapy regimen (QUAD SHOT) in previously untreated patients with incurable squamous cell carcinoma of the head and neck. Secondary objectives were to prospectively evaluate toxicity, quality of life (QoL) and survival in these patients. PATIENTS AND METHODS: The QUAD SHOT consisted of 14 Gy in four fractions, given twice a day and at least 6h apart, for 2 consecutive days. This regimen was repeated at 4 weekly intervals for a further two courses if there was no tumour progression. The QoL tool used was an abbreviation of the EORTC QLQ-C30. RESULTS: Thirty eligible patients (29 Stage IV, 20 performance status 2-3) had at least one treatment and 16 patients completed all three cycles. Sixteen patients (53%) had an objective response (2CR, 14PR) and a further seven had stable disease. Median overall survival was 5.7 months, median progression free survival was 3.1 months. The treatment was very well tolerated, with improved QoL in 11 of 25 evaluable patients (44%). CONCLUSION: The QUAD SHOT regimen is an effective palliative treatment with minimal toxicity and a good response rate, which impacts positively on patients' QoL. 相似文献
48.
Bojan Lalovic Brian Phillips Linda L Risler William Howald Danny D Shen 《Drug metabolism and disposition》2004,32(4):447-454
Oxycodone undergoes N-demethylation to noroxycodone and O-demethylation to oxymorphone. The cytochrome P450 (P450) isoforms capable of mediating the oxidation of oxycodone to oxymorphone and noroxycodone were identified using a panel of recombinant human P450s. CYP3A4 and CYP3A5 displayed the highest activity for oxycodone N-demethylation; intrinsic clearance for CYP3A5 was slightly higher than that for CYP3A4. CYP2D6 had the highest activity for O-demethylation. Multienzyme, Michaelis-Menten kinetics were observed for both oxidative reactions in microsomes prepared from five human livers. Inhibition with ketoconazole showed that CYP3A is the high affinity enzyme for oxycodone N-demethylation; ketoconazole inhibited >90% of noroxycodone formation at low substrate concentrations. CYP3A-mediated noroxycodone formation exhibited a mean K(m) of 600 +/- 119 microM and a V(max) that ranged from 716 to 14523 pmol/mg/min. Contribution from the low affinity enzyme(s) did not exceed 8% of total intrinsic clearance for N-demethylation. Quinidine inhibition showed that CYP2D6 is the high affinity enzyme for O-demethylation with a mean K(m) of 130 +/- 33 microM and a V(max) that ranged from 89 to 356 pmol/mg/min. Activity of the low affinity enzyme(s) accounted for 10 to 26% of total intrinsic clearance for O-demethylation. On average, the total intrinsic clearance for noroxycodone formation was 8 times greater than that for oxymorphone formation across the five liver microsomal preparations (10.5 microl/min/mg versus 1.5 microl/min/mg). Experiments with human intestinal mucosal microsomes indicated lower N-demethylation activity (20-50%) compared with liver microsomes and negligible O-demethylation activity, which predict a minimal contribution of intestinal mucosa in the first-pass oxidative metabolism of oxycodone. 相似文献
49.
50.