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101.
Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity 下载免费PDF全文
Azmy IA Balasubramanian SP Wilson AG Stephenson TJ Cox A Brown NJ Reed MW 《Breast cancer research : BCR》2004,6(4):R395-R400
Introduction
Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study. 相似文献102.
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Huang B Sikorski R Sampath P Thorne SH 《Journal of immunotherapy (Hagerstown, Md. : 1997)》2011,34(3):289-296
A variety of immune cell therapies proposed for use in the treatment of cancer, including both autologous cells (Lymphokine Activated Killer, Cytokine Induced Killer) or cell lines (TALL-104, NK-92), rely on recognition of NKG2D ligands on malignant cells for targeting. These ligands, such as MICA and MICB in humans are stress response ligands and are commonly, but not ubiquitously expressed within tumors. Several tumor escape mechanisms have been reported, including ligand downregulation and internalization, or proteolytic cleavage and shedding of their exposed portions (releasing soluble MICA and MICB; sMICA, sMICB). Therefore, an ability to prescreen patients for the level of tumor cell surface expression and shedding of these ligands would prevent needless treatment of patients that are unable to respond, whereas targeted pretreatment of patients to increase surface expression and/or block shedding would enhance the subsequent effectiveness of these therapies. Here, we report that serum tests of sMICA and sMICB in conjunction with tumor measurements might be used to determine rates of shedding from a tumor and that treatment with a selected combination of histone deacetylase inhibitors (to upregulate cell surface MICA/B in some tumors), and metalloproteinase inhibitors (to block MICA/B shedding in others) can be incorporated to regulate cell surface MICA/B levels before immune cell therapy, significantly enhancing their effectiveness (either used alone or as carrier vehicles for oncolytic viruses). Ultimately prescreening patients undergoing such immune cell therapies might be used to personalize cancer treatment regimens based on the NKG2D-ligand status of the tumor. 相似文献
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RH De Boer D Kotasek S White B Koczwara P Mainwaring A Chan R Melara Y Ye AH Adewoye R Sikorski PA Kaufman 《Breast cancer research and treatment》2012,135(1):241-252
The purpose of this study was to investigate the safety, tolerability, and pharmacokinetics of motesanib when combined with docetaxel or paclitaxel in patients with metastatic breast cancer. In this open-label, dose-finding, phase 1b study, patients received motesanib 50 or 125-mg orally once daily (QD), beginning day 3 of cycle 1 of chemotherapy, continuously in combination with either paclitaxel 90 mg/m2 on days 1, 8, and 15 every 28-day cycle (Arm A) or docetaxel 100 mg/m2 on day 1 every 21-day cycle (Arm B). Dose escalation to motesanib 125 mg QD occurred if the incidence of dose-limiting toxicities (DLTs, primary endpoint) was ≤33 %. If the maximum tolerated dose (MTD) of motesanib was established in Arm B, additional patients could receive motesanib at the MTD plus docetaxel 75 mg/m2. Forty-six patients were enrolled and 45 received ≥1 dose of motesanib. The incidence of DLTs was <33 % in all cohorts; thus, motesanib 125 mg QD was established as the MTD. Seven patients (16 %) had grade 3 motesanib-related adverse events including cholecystitis (2 patients) and hypertension (2 patients). Pharmacokinetic parameters of motesanib were similar to those reported in previous studies. The objective response rate was 56 % among patients with measurable disease at baseline who received motesanib in combination with taxane-based chemotherapy. The addition of motesanib to either paclitaxel or docetaxel was generally tolerable up to the 125-mg QD dose of motesanib. The objective response rate of 56 % suggests a potential benefit of motesanib in combination with taxane-based chemotherapy. 相似文献
106.
Fábio S Lira José C Rosa Gustavo D Pimentel Victor AF Tarini Ricardo M Arida Flávio Faloppa Eduardo S Alves Cláudia O do Nascimento Lila M Oyama Marília Seelaender Marco T de Mello Ronaldo VT Santos 《Lipids in health and disease》2010,9(1):1-10
Introduction
Cytokines (IL-6, IL-10 and TNF-α) are increased after exhaustive exercise in the rat retroperitoneal (RPAT) and mesenteric adipose tissue (MEAT) pads. On the other hand, these cytokines show decreased expression in these depots in response to a chronic exercise protocol. However, the effect of exercise with overload combined with a short recovery period on pro- and anti-inflammatory cytokine expression is unknown. In the present study, we investigated the regulation of cytokine production in the adipose tissue of rats after an overtraining-inducing exercise protocol.Methods
Male Wistar rats were divided into four groups: Control (C), Trained (Tr), Overtrained (OT) and recovered overtrained (R). Cytokines (IL-6, TNF-α and IL-10) levels and Toll Like Receptor 4 (TLR4), Nuclear Factor kBp65 (NF-kBp65), Hormone Sensitive Lipase (HSL) and, Perilipin protein expression were assessed in the adipose tissue. Furthermore, we analysed plasma lipid profile, insulin, testosterone, corticosterone and endotoxin levels, and liver triacylglycerol, cytokine content, as well as apolipoprotein B (apoB) and TLR4 expression in the liver.Results
OT and R groups exhibited reduced performance accompanied by lower testosterone and increased corticosterone and endotoxin levels when compared with the control and trained groups. IL-6 and IL-10 protein levels were increased in the adipose tissue of the group allowed to recover, in comparison with all the other studied groups. TLR-4 and NF-kBp65 were increased in this same group when compared with both control and trained groups. The protein expression of HSL was increased and that of Perilipin, decreased in the adipose in R in relation to the control. In addition, we found increased liver and serum TAG, along with reduced apoB protein expression and IL-6 and IL-10 levels in the of R in relation to the control and trained groups.Conclusion
In conclusion, we have shown that increases in pro-inflammatory cytokines in the adipose tissue after an overtraining protocol may be mediated via TLR-4 and NF-kBp65 signalling, leading to an inflammatory state in this tissue. 相似文献107.
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Mandy B Belfort John AF Zupancic Katherine M Riera Jane HG Turner Lisa A Prosser 《BMC pediatrics》2011,11(1):12