全文获取类型
收费全文 | 3528篇 |
免费 | 299篇 |
国内免费 | 249篇 |
专业分类
耳鼻咽喉 | 22篇 |
儿科学 | 49篇 |
妇产科学 | 46篇 |
基础医学 | 425篇 |
口腔科学 | 75篇 |
临床医学 | 481篇 |
内科学 | 497篇 |
皮肤病学 | 28篇 |
神经病学 | 188篇 |
特种医学 | 192篇 |
外国民族医学 | 1篇 |
外科学 | 325篇 |
综合类 | 478篇 |
一般理论 | 1篇 |
预防医学 | 240篇 |
眼科学 | 96篇 |
药学 | 406篇 |
3篇 | |
中国医学 | 178篇 |
肿瘤学 | 345篇 |
出版年
2024年 | 8篇 |
2023年 | 29篇 |
2022年 | 100篇 |
2021年 | 153篇 |
2020年 | 95篇 |
2019年 | 109篇 |
2018年 | 130篇 |
2017年 | 99篇 |
2016年 | 80篇 |
2015年 | 139篇 |
2014年 | 168篇 |
2013年 | 178篇 |
2012年 | 231篇 |
2011年 | 270篇 |
2010年 | 165篇 |
2009年 | 167篇 |
2008年 | 154篇 |
2007年 | 191篇 |
2006年 | 201篇 |
2005年 | 208篇 |
2004年 | 123篇 |
2003年 | 150篇 |
2002年 | 106篇 |
2001年 | 102篇 |
2000年 | 87篇 |
1999年 | 90篇 |
1998年 | 76篇 |
1997年 | 72篇 |
1996年 | 66篇 |
1995年 | 58篇 |
1994年 | 38篇 |
1993年 | 22篇 |
1992年 | 25篇 |
1991年 | 9篇 |
1990年 | 25篇 |
1989年 | 31篇 |
1988年 | 33篇 |
1987年 | 21篇 |
1986年 | 12篇 |
1985年 | 6篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 9篇 |
1981年 | 5篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1975年 | 5篇 |
1959年 | 1篇 |
排序方式: 共有4076条查询结果,搜索用时 15 毫秒
991.
992.
NTRODUCTIONTheefectoftraditionalyinhalationalanesthetichalothaneandnewdrugsevofluraneonmitochondrialmembraneisreportedbelowi... 相似文献
993.
994.
Population pharmacokinetics of tacrolimus in whole blood and plasma in asian liver transplant patients 总被引:2,自引:0,他引:2
Sam WJ Tham LS Holmes MJ Aw M Quak SH Lee KH Lim SG Prabhakaran K Chan SY Ho PC 《Clinical pharmacokinetics》2006,45(1):59-75
OBJECTIVES: The objectives of this study were to develop population pharmacokinetic models of tacrolimus in an Asian population with whole blood and plasma drug concentration data, to compare the variability of the pharmacokinetic parameters in these two matrices and to search for the main patient characteristics that explain the variability in pharmacokinetic parameters. STUDY DESIGN: Prospective pharmacokinetic assessment followed by model fitting. PATIENTS: Whole blood samples from 31 liver transplant patients in a local hospital receiving oral tacrolimus as part of their immunosuppressive therapy were assessed. Plasma samples from 29 of the 31 patients were also evaluated. Concentrations of tacrolimus in whole blood and plasma were determined by an electrospray high-performance liquid chromatography with tandem mass spectrometry. Two hundred and thirteen whole blood and 157 plasma tacrolimus concentrations were used for building two nonlinear mixed-effects population models to describe the disposition of tacrolimus in whole blood and plasma, respectively. Covariates that were investigated included demographic characteristics, biological markers of liver and renal functions, corticosteroid dose and haematological parameter. RESULTS: A one-compartment model was used to describe the whole blood and plasma concentration-time data of tacrolimus after oral administration. For the whole blood population model, the population estimates of the first-order absorption rate constant (k(a)), apparent clearance based on whole blood concentration after oral administration (CL(B)/F) and apparent volume of distribution based on whole blood concentrations after oral administration (V(d,B)/F) were 2.08h(-1), 14.1 L/h and 217L, respectively. The coefficient of variations (CVs) of interpatient variabilities in CL(B)/F and V(d,B)/F were 65.7% and 63.8%, respectively. Bodyweight, liver and renal function influenced CL(B)/F, while height and haematocrit influenced V(d,B)/F. The residual (unexplained) variability was 34.8%. For the plasma population model, the population estimates of the k(a), apparent clearance based on plasma concentrations after oral administration (CL(P)/F) and apparent volume of distribution based on plasma concentrations after oral administration (V(d,P)/F) were 5.21h(-1), 537 L/h and 563L, respectively. The CVs of interpatient variabilities in CL(P)/F and V(d,P)/F were 96.0% and 105.4%, respectively. Bodyweight was found to influence CL(P)/F, while the erythrocyte-to-plasma concentration ratio influenced V(d,P)/F. The residual (unexplained) variability was 49.8% at the mean plasma concentration of 1.1 ng/mL. CONCLUSIONS: Whole blood and plasma population pharmacokinetic models of tacrolimus in Asian adult and paediatric liver transplant patients were developed using prospective data in a clinical setting. This has identified and quantified sources of interindividual variability in CL(B)/F, V(d,B)/F, CL(P)/F and V(d,P)/F of tacrolimus in Asian liver transplant patients. Information derived from the whole blood population model may subsequently be used by clinicians for dosage individualisation through Bayesian forecasting. 相似文献
995.
Zhang HZ Zhang H Kemnitzer W Tseng B Cinatl J Michaelis M Doerr HW Cai SX 《Journal of medicinal chemistry》2006,49(3):1198-1201
This paper describes the design and synthesis of dipeptidyl N,N-dimethyl glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV-induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk (6a) was found to be a potent inhibitor with low toxicity in cells, protecting cells with an EC(50) value of 2.5 microM and exhibiting a selectivity index of >40. 相似文献
996.
Sui M Chen F Chen Z Fan W 《International journal of cancer. Journal international du cancer》2006,119(3):712-717
Paclitaxel is a widely used naturally occurring antineoplastic agent that has shown great promise in the treatment of a variety of human solid tumors, particularly for advanced breast and ovarian cancers. Recent studies in our laboratory discovered that glucocorticoids could selectively inhibit paclitaxel-induced apoptosis in a number of human solid tumor cell lines in vitro. Since glucocorticoids (such as dexamethasone) are routinely used as a premedication in the clinical application of paclitaxel to prevent hypersensitivity reactions and other adverse effects, the inhibitory effect of glucocorticoids on paclitaxel-induced apoptosis has raised a clinically relevant question as to whether the pretreatment with glucocorticoids might interfere with the therapeutic efficacy of paclitaxel. In the present study, through development of animal models bearing human breast and ovarian xenograft tumors, we evaluated the potential influence of dexamethasone on antitumor activity of paclitaxel in vivo. The results demonstrated that pretreatment of dexamethasone significantly attenuated therapeutic efficacy of paclitaxel against human breast and ovarian xenograft tumors. The inhibition rate of 20 mg paclitaxel/kg on the growth of breast and ovarian xenograft tumors was around 20-25% less when the animals were pretreated with 1 mg dexamethasone/kg. Further analyses with histological examination and TdT-mediated dUTP nick end labeling assay indicate that pretreatment with dexamethasone clearly interferes with the cytotoxic effects of paclitaxel on both morphological alterations and induction of cell death. Additionally, immunohistochemical staining of proliferation marker Ki-67 indicates that the percentage of proliferating cells in xenograft tumors with pretreatment of dexamethasone is much higher than that in the tumors treated with paclitaxel alone. Put together, the results obtained from the animal experiments show that pretreatment of xenograft tumors with dexamethasone results in significant inhibition of the therapeutic efficacy of paclitaxel in vivo. This finding may have a potential implication on the clinical practice of paclitaxel-based chemotherapy. 相似文献
997.
Primary antibody response to keyhole limpet hemocyanin in rat as a model for immunotoxicity evaluation 总被引:1,自引:0,他引:1
To address current regulatory expectations on immunotoxicity testing of new chemicals, we describe an animal model that measures the primary antibody response to the T-cell dependent antigen, keyhole limpet hemocyanin (KLH). Single immunization with KLH by either footpad (300microg/rat) or intravenous (300microg/kg) route in Sprague Dawley rats resulted in increased germinal center formation in the spleen and a robust anti-KLH IgM (70-388microg/ml) and IgG (230-470microg/ml) antibody response with peak detection on Days 5 and 14 post-immunization, respectively. Subcutaneous immunization with KLH (300microg/kg) resulted in a much weaker anti-KLH IgM and IgG (< or =20microg/ml) antibody response with no detectable increase in splenic germinal center formation. The utility of a rat KLH immunization model in detecting immunosuppression was evaluated with the known immunosuppressive drugs: cyclosporin, azathioprine and prednisolone. Rats, treated with drug at a maximum tolerated dose, were immunized with KLH by footpad or intravenous injection and serum samples were collected at various intervals up to 2 weeks post-immunization. Additional study parameters included terminal body weight, hematology and/or histopathology. All three drugs inhibited the IgM (60%) and IgG (> or =90%) antibody responses in the absence of overt toxicity based on evaluation of the standard toxicology parameters. In conclusion, measurement of a rat primary antibody response to KLH by ELISA is a reliable and readily standardized method for assessing immunotoxicity of pharmaceuticals. 相似文献
998.
目的 探讨补肾益气方对正常早孕期人细胞滋养层细胞增殖、侵袭、分化等生物学行为的影响。方法 体外培养正常早孕期人细胞滋养层细胞,分别设空白对照组、5%含药血清组、10%含药血清组、20%含药血清组,用扫描电镜、噻唑蓝(MTT)法、流式细胞仪、Transwell侵袭实验检测含药血清作用24h、48h、72h后细胞的形态、增殖活性及侵袭力的变化。结果 含药血清培养24h、48h、72h后,细胞滋养层细胞微绒毛变丰富,伪足增多、延长;细胞在酶联免疫分析仪490nm波长的吸光度值增加(P<0.01);sub-G1期细胞减少(P<0.01),S期细胞增加(P<0.01),G2/M期细胞明显减少(P<0.01);每视野穿过PET膜的细胞数明显增多(P<0.01)。结论 补肾中药促进人细胞滋养层细胞增殖及侵袭力,并可能影响其分化能力。 相似文献
999.
1000.
St. John’s Wort Modulates the Toxicities and Pharmacokinetics of CPT-11 (Irinotecan) in Rats 总被引:1,自引:0,他引:1
Hu Z Yang X Ho PC Chan E Chan SY Xu C Li X Zhu YZ Duan W Chen X Huang M Yang H Zhou S 《Pharmaceutical research》2005,22(6):902-914
CPT-11 is a DNA topoisomerase I inhibitor for the therapy of colorectal cancer, whereas St. Johns Wort (Hypericum perforatum, SJW) is a widely used herbal anti-depressant. This study aimed to investigate the effects of co-administered SJW on the toxicities and pharmacokinetics of CPT-11 and the underlying mechanisms. The body weight loss, gastrointestinal and hematological toxicities induced by CPT-11, and the pharmacokinetic parameters of CPT-11 were evaluated in rats pretreated with SJW or vehicle. Rats treated with CPT-11 alone experienced rapid decrease in body weight, whereas co-administration of SJW with CPT-11 resulted in lesser body weight loss. The gastrointestinal and hematological toxicities following CPT-11 injection were both alleviated in the presence of SJW. The rat pharmacokinetics of both CPT-11 and its metabolite SN-38 were significantly altered in presence of SJW. In conclusion, co-administered SJW significantly ameliorated the toxicities induced by CPT-11. The protective effect of SJW may be partially due to pharmacokinetic interaction between CPT-11 and SJW. 相似文献