全文获取类型
收费全文 | 2076篇 |
免费 | 119篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 9篇 |
儿科学 | 35篇 |
妇产科学 | 45篇 |
基础医学 | 375篇 |
口腔科学 | 33篇 |
临床医学 | 194篇 |
内科学 | 417篇 |
皮肤病学 | 34篇 |
神经病学 | 217篇 |
特种医学 | 136篇 |
外科学 | 195篇 |
综合类 | 13篇 |
一般理论 | 2篇 |
预防医学 | 173篇 |
眼科学 | 30篇 |
药学 | 139篇 |
中国医学 | 9篇 |
肿瘤学 | 149篇 |
出版年
2024年 | 2篇 |
2023年 | 20篇 |
2022年 | 44篇 |
2021年 | 68篇 |
2020年 | 35篇 |
2019年 | 53篇 |
2018年 | 72篇 |
2017年 | 53篇 |
2016年 | 56篇 |
2015年 | 65篇 |
2014年 | 95篇 |
2013年 | 137篇 |
2012年 | 198篇 |
2011年 | 181篇 |
2010年 | 98篇 |
2009年 | 80篇 |
2008年 | 153篇 |
2007年 | 149篇 |
2006年 | 133篇 |
2005年 | 126篇 |
2004年 | 102篇 |
2003年 | 90篇 |
2002年 | 81篇 |
2001年 | 16篇 |
2000年 | 3篇 |
1999年 | 14篇 |
1998年 | 15篇 |
1997年 | 9篇 |
1996年 | 9篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 6篇 |
1992年 | 6篇 |
1991年 | 6篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1974年 | 2篇 |
1965年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有2205条查询结果,搜索用时 15 毫秒
991.
992.
Herzig MC Kolly C Persohn E Theil D Schweizer T Hafner T Stemmelen C Troxler TJ Schmid P Danner S Schnell CR Mueller M Kinzel B Grevot A Bolognani F Stirn M Kuhn RR Kaupmann K van der Putten PH Rovelli G Shimshek DR 《Human molecular genetics》2011,20(21):4209-4223
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset Parkinson's disease (PD), but the underlying pathophysiological mechanisms and the normal function of this large multidomain protein remain speculative. To address the role of this protein in vivo, we generated three different LRRK2 mutant mouse lines. Mice completely lacking the LRRK2 protein (knock-out, KO) showed an early-onset (age 6 weeks) marked increase in number and size of secondary lysosomes in kidney proximal tubule cells and lamellar bodies in lung type II cells. Mice expressing a LRRK2 kinase-dead (KD) mutant from the endogenous locus displayed similar early-onset pathophysiological changes in kidney but not lung. KD mutants had dramatically reduced full-length LRRK2 protein levels in the kidney and this genetic effect was mimicked pharmacologically in wild-type mice treated with a LRRK2-selective kinase inhibitor. Knock-in (KI) mice expressing the G2019S PD-associated mutation that increases LRRK2 kinase activity showed none of the LRRK2 protein level and histopathological changes observed in KD and KO mice. The autophagy marker LC3 remained unchanged but kidney mTOR and TCS2 protein levels decreased in KD and increased in KO and KI mice. Unexpectedly, KO and KI mice suffered from diastolic hypertension opposed to normal blood pressure in KD mice. Our findings demonstrate a role for LRRK2 in kidney and lung physiology and further show that LRRK2 kinase function affects LRRK2 protein steady-state levels thereby altering putative scaffold/GTPase activity. These novel aspects of peripheral LRRK2 biology critically impact ongoing attempts to develop LRRK2 selective kinase inhibitors as therapeutics for PD. 相似文献
993.
Dragica ManojlovicMarina Radisic Tatjana VasiljevicSlavoljub Zivkovic Mila LausevicVesna Miletic 《Dental materials》2011,27(4):371-378
Objectives
To study monomer elution from four resin-based composites (RBCs) cured with different light sources.Methods
Twenty-eight premolars were randomly allocated to four groups. Standardized cavities were prepared and restored with a nanohybrid (Filtek Supreme XT or Tetric EvoCeram), an ormocer (Admira) or a microhybrid RBC (Filtek Z250) which served as control. Buccal restorations were cured with a halogen and oral restorations with an LED light-curing unit. Elution of diurethane dimethacrylate (UDMA), Bisphenol A diglycidylether methacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA) and 2-hydroxyethyl methacrylate (HEMA) was analyzed using high-performance liquid chromatography (HPLC) 1 h to 28 days post-immersion in 75% ethanol. Data were analyzed using multivariate and repeated measures analysis of variance (α = 0.05).Results
The greatest elution of UDMA and BisGMA occurred from Tetric EvoCeram and the least from Filtek Z250 (p < 0.05). LED and halogen light-curing units gave similar results for all RBCs (p > 0.05) except Tetric EvoCeram which showed greater elution for the LED unit (p < 0.05). TEGDMA was below the limit of quantification. HEMA eluted in similar concentrations from Filtek Supreme and Tetric EvoCeram (p > 0.05).Significance
: The two nanohybrid RBCs eluted more cross-linking monomers than the ormocer and the control microhybrid RBC. Continuous elution over 28 days indicates that RBCs act as a chronic source of monomers in clinical conditions. Light source may affect monomer elution since differences were found for one out of four RBCs. Mathematical models for elution kinetics of UDMA and BisGMA indicated two elution mechanisms. 相似文献994.
995.
Objectives
The objective of this paper is to assess the suitability of brain function monitors for use in closed-loop anesthesia or sedation delivery. In such systems, monitors used as feedback sensors should preferably be Linear and Time Invariant (LTI) in order to limit sensor-induced uncertainty which can cause degraded performance. In this paper, we evaluate the suitability of the BIS A2000 (Aspect Medical Systems, MA), the M-Entropy Monitor (GE HealthCare), and the NeuroSENSE Monitor (NeuroWave Systems Inc, OH), by verifying whether their dynamic behavior conforms to the LTI hypothesis. 相似文献996.
J. Radovic D. Maksimovic-Ivanic G. Timotijevic S. Popadic Z. Ramic V. Trajkovic D. Miljkovic S. Stosic-Grujicic S. Mijatovic 《Food and chemical toxicology》2012
Intrinsic characteristics of melanoma cells such as expression of inducible nitric oxide synthase (iNOS), redox status, and activity of signaling pathways involved in proliferation, differentiation and cell death define the response of the cells to the diverse treatments. In this context we compared the effectiveness of herbal antaquinone aloe emodin (AE) against mouse B16 melanoma and human A375, different in initial activity of ERK1/2, constitutive iNOS expression and basal level of reactive oxygen species (ROS). Both cell lines are sensitive to AE treatment. However, while the agent induces differentiation of B16 cells toward melanocytes, in A375 cells promoted massive apoptosis. Differentiation of B16 cells, characterized by enhanced melanin production and tyrosinase activity, was mediated by H2O2 production synchronized with rapid p53 accumulation and enhanced expression of cyclins D1 and D3. Caspase mediated apoptosis triggered in A375 cells was accompanied with Bcl-2 but not iNOS down-regulation. In addition, opposite regulation of Akt-ERK1/2 axis in AE treated B16 and A375 cells correlated with different outcome of the treatment. However, AE in a dose-dependent manner rescued both B16 and A375 cells from doxorubicin- or paclitaxel-induced killing. These data indicate that caution is warranted when AE is administrated to the patients with conventional chemotherapy. 相似文献
997.
998.
Ferroni P Della-Morte D Palmirotta R McClendon M Testa G Abete P Rengo F Rundek T Guadagni F Roselli M 《Rejuvenation research》2011,14(3):293-308
Cancer in elderly patients is an increasingly common problem. Older patients have more co-morbidity, therefore the toxic effects of chemotherapy treatment are less tolerable compared to younger patients. Platinum-based compounds (PBCs) are commonly used cytotoxic agents in the treatment of several solid tumors; however, their application is still limited in elderly patients, due to the risks in cardiovascular toxicity. The increased risk for myocardial ischemia, stroke, and vascular thrombosis linked with PBCs treatment is mainly due to reactive oxygen species (ROS) production and the subsequent induction of oxidative stress and switch to a prothrombotic condition. Recently, studies have shown a different genetic susceptibility in cardiovascular toxicity induced by therapy with PBCs. Antioxidants, such as vitamin E, selenium, lycopene, melatonin, and resveratrol, have been implicated in cancer treatment by their property to suppress the oxidant injury. Resveratrol, especially, has been shown to increase the antineoplastic activity of cisplatin. In addition, resveratrol's ability to activate the sirtuin1 (SIRT1) pathway has been heavily implicated in the mechanisms controlling longevity and quality of life in the aged population. This article reviews the current state of treatment with PBCs and their associated risk for cardiovascular disease. It discusses the most powerful antioxidant supplementation options as a possible strategy to reduce the cardiovascular toxicity effects of chemotherapy in the elderly. 相似文献
999.
Stefan Farese Emilie Stauffer Robert Kalicki Tatjana Hildebrandt Brigitte M. Frey Felix J. Frey Dominik E. Uehlinger Andreas Pasch 《Clinical journal of the American Society of Nephrology》2011,6(6):1447-1455
Summary
Background and objectives
Vascular calcification is a major cause of morbidity and mortality in dialysis patients. Human and animal studies indicate that sodium thiosulfate (STS) may prevent the progression of vascular calcifications. The pharmacokinetics of STS in hemodialysis patients has not been investigated yet.Design, setting, participants, & measurements
STS was given intravenously to 10 hemodialysis patients on- and off-hemodialysis. Additionally, STS was applied to 9 healthy volunteers once intravenously and once orally. Thiosulfate concentrations were measured by using a specific and sensitive HPLC method.Results
In volunteers and patients, mean endogenous thiosulfate baseline concentrations were 5.5 ± 1.82 versus 7.1 ± 2.7 μmol/L. Renal clearance was high in volunteers (1.86 ± 0.45 ml/min per kg) and reflected GFR. Nonrenal clearance was slightly, but not significantly, higher in volunteers (2.25 ± 0.32 ml/min per kg) than in anuric patients (2.04 ± 0.72 ml/min per kg). Hemodialysis clearance of STS was 2.62 ± 1.01 ml/min per kg. On the basis of the nonrenal clearance and the thiosulfate steady-state serum concentrations, a mean endogenous thiosulfate generation rate of 14.6 nmol/min per kg was calculated in patients. After oral application, only 4% of STS was recovered in urine of volunteers, reflecting a low bioavailability of 7.6% (0.8% to 26%).Conclusions
Given the low and variable bioavailability of oral STS, only intravenous STS should be prescribed today. The biologic relevance of the high hemodialysis clearance for the optimal time point of STS dosing awaits clarification of the mechanisms of action of STS. 相似文献1000.
Pinkus Tober-Lau Tatjana Schwarz David Hillus Jana Spieckermann Elisa T. Helbig Lena J. Lippert Charlotte Thibeault Willi Koch Leon Bergfeld Daniela Niemeyer Barbara Mühlemann Claudia Conrad Stefanie Kasper Friederike Münn Frank Kunitz Terry C. Jones Norbert Suttorp Christian Drosten Leif Erik Sander Florian Kurth Victor M. Corman 《Emerging infectious diseases》2021,27(8):2169
One week after second vaccinations were administered, an outbreak of B.1.1.7 lineage severe acute respiratory syndrome coronavirus 2 infections occurred in a long-term care facility in Berlin, Germany, affecting 16/20 vaccinated and 4/4 unvaccinated residents. Despite considerable viral loads, vaccinated residents experienced mild symptoms and faster time to negative test results. 相似文献