全文获取类型
收费全文 | 5449篇 |
免费 | 383篇 |
国内免费 | 59篇 |
专业分类
耳鼻咽喉 | 32篇 |
儿科学 | 134篇 |
妇产科学 | 137篇 |
基础医学 | 802篇 |
口腔科学 | 113篇 |
临床医学 | 478篇 |
内科学 | 1278篇 |
皮肤病学 | 153篇 |
神经病学 | 663篇 |
特种医学 | 205篇 |
外科学 | 479篇 |
综合类 | 8篇 |
一般理论 | 1篇 |
预防医学 | 297篇 |
眼科学 | 58篇 |
药学 | 402篇 |
中国医学 | 26篇 |
肿瘤学 | 625篇 |
出版年
2024年 | 11篇 |
2023年 | 90篇 |
2022年 | 178篇 |
2021年 | 310篇 |
2020年 | 197篇 |
2019年 | 252篇 |
2018年 | 235篇 |
2017年 | 175篇 |
2016年 | 205篇 |
2015年 | 227篇 |
2014年 | 264篇 |
2013年 | 343篇 |
2012年 | 490篇 |
2011年 | 454篇 |
2010年 | 230篇 |
2009年 | 217篇 |
2008年 | 362篇 |
2007年 | 343篇 |
2006年 | 318篇 |
2005年 | 244篇 |
2004年 | 242篇 |
2003年 | 197篇 |
2002年 | 165篇 |
2001年 | 26篇 |
2000年 | 12篇 |
1999年 | 13篇 |
1998年 | 28篇 |
1997年 | 12篇 |
1996年 | 12篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 5篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有5891条查询结果,搜索用时 265 毫秒
941.
Krishnaraj Rathod Vikas Kapil Shanti Velmurugan Rayomand Khambata Umme Siddique Saima Khan Lorna Gee Jaspal Bansal Kavi Pitrola Christopher Shaw Fulvio DAcquisto Romain Colas Federica Marelli-Berg Jesmond Dalli Amrita Ahluwalia 《Lancet》2017
Background
Premenopausal women have a lower incidence of cardiovascular disease, although the exact mechanism underlying this protection is unclear. Both systemic and localised inflammation have a crucial role in the progression of cardiovascular disease, and much preclinical and observational data in human beings suggest that differences in inflammation between the sexes exist. We investigated whether inflammation, and which components of the inflammatory response, might be altered in women compared with men.Methods
We performed two clinical studies with 24 and 32 healthy volunteers. In 12 men and 12 women (mean age 26·0 years [SD 5·7] and 24·7 [6·8], respectively), we assessed systemic inflammatory markers and vascular function using brachial artery flow-mediated dilation (FMD) determined with ultrasound. Responses were assessed before administration of typhoid vaccine and then at 8 h and 32 h afterwards. In another study, in 16 male and 16 female volunteers (mean age 27·4 years [SD 1·1] and 26·8 [1·1], respectively), inflammatory exudate and cellular recruitment were measured at 24 h (acute) and 72 h (resolution) in skin blisters induced with cantharidin. Ethics approval was given by NRES: City Road and Hampstead Ethics Committee (11/LO/2038) for both studies. Both studies are registered with ClinicalTrials.gov, number NCT01582321.Findings
Typhoid vaccine caused a mild systemic inflammation, which was associated with a trend to decreased FMD in men and an increased response in women compared with baseline (p=0·006). By 24 h cantharidin induced a fluid-filled blister of a similar volume in both sexes; however, after 72 h blisters had resolved only in women (p=0·003). At 24 h there was a significant reduction in both monocyte (p=0·003) and lymphocyte count (p=0·011) in blisters in women compared with those in men. A generalised reduction in the activation state of all major leucocytes including neutrophils was evident in women. These differences in cell recruitment and activation were associated with higher proresolving mediators, including the D-resolvins, and a reduction in concentrations of the neutrophil chemoattractant leukotriene B4.Interpretation
Our findings suggest that female sex protects against endothelial dysfunction induced by systemic inflammation. This effect is probably due to a rapid resolution of inflammation in women specifically targeting the neutrophil through elevation of the D-resolvin pathway.Funding
KR receives doctoral research fellowship funding from the National Institute for Health Research. JD receives funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement 677542), and is also supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant 107613/Z/15/Z). 相似文献942.
943.
944.
Luca Elli Federica Branchi Carolina Tomba Danilo Villalta Lorenzo Norsa Francesca Ferretti Leda Roncoroni Maria Teresa Bardella 《World journal of gastroenterology : WJG》2015,21(23):7110-7119
Cereal crops and cereal consumption have had a vital role in Mankind's history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient's clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis. 相似文献
945.
Pier Paolo Mainenti Federica Romano Laura Pizzuti Sabrina Segreto Giovanni Storto Lorenzo Mannelli Massimo Imbriaco Luigi Camera Simone Maurea 《World journal of radiology》2015,7(7):157-169
Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver-directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs. 相似文献
946.
Barbieri F Würth R Favoni RE Pattarozzi A Gatti M Ratto A Ferrari A Bajetto A Florio T 《Biochemical pharmacology》2011,(10):1542-1477
Malignant pleural mesothelioma (MPM) is an aggressive chemotherapy-resistant cancer. Up-regulation of epidermal growth factor receptor (EGFR) plays an important role in MPM development and EGFR-tyrosine kinase inhibitors (TKIs) may represent novel therapeutic options. We tested the effects of the EGFR TKIs gefitinib and erlotinib and TKIs targeted to other growth factors (VEGFR and PDGFR), in comparison to standard antineoplastic agents, in two human MPM cell lines, IST-Mes2 and ZL55. All drugs showed IC50 values in the micromolar range: TKIs induced cytostatic effects at concentrations up to the IC50, while conventional drug growth-inhibitory activity was mainly cytotoxic. Moreover, the treatment of IST-Mes2 with TKIs (gefitinib and imatinib mesylate) in combination with cisplatin and gemcitabine did not show additivity. Focusing on the molecular mechanisms underlying the antiproliferative and pro-apoptotic effects of EGFR-TKIs, we observed that gefitinib induced the formation and stabilization of inactive EGFR homodimers, even in absence of EGF, as demonstrated by EGFR Bmax and number of sites/cell. The analysis of downstream effectors of EGFR signaling demonstrated that EGF-induced proliferation, reverted by gefitinib, involved ERK1/2 activation, independently from Akt pathway. Gefitinib inhibits MPM cell growth and survival, preventing EGF-dependent activation of ERK1/2 pathway by blocking EGFR-TK phosphorylation and stabilizing inactive EGFR dimers. Along with the molecular definition of TKIs pharmacological efficacy in vitro, these results may contribute to delve deep into the promising but still controversial role for targeted and conventional drugs in the therapy of MPM. 相似文献
947.
Lince F Bolognesi S Marchisio DL Stella B Dosio F Barresi AA Cattel L 《Journal of pharmaceutical sciences》2011,100(6):2391-2405
In this work, the biodegradable copolymer poly(methoxypolyethyleneglycolcyanoacrylate-co-hexadecylcyanoacrylate) is used to prepare nanoparticles via solvent displacement in a confined impinging jets reactor (CIJR). For comparison, nanoparticles constituted by the homopolymer counterpart are also investigated. The CIJR is a small passive mixer in which very fast turbulent mixing of the solvent (i.e., acetone and tetrahydrofuran) and of the antisolvent (i.e., water) solutions occurs under controlled conditions. The effect of the initial copolymer concentration, solvent type, antisolvent-to-solvent ratio, and mixing rate inside the mixer on the final nanoparticle size distribution, surface properties, and morphology is investigated from the experimental point of view. The effect of some of these parameters is studied by means of a computational fluid dynamics (CFD) model, capable of quantifying the mixing conditions inside the CIJR. Results show that the CIJR can be profitably used for producing nanoparticles with controlled characteristics, that there is a clear correlation between the mixing rate calculated by CFD and the mean nanoparticle size, and therefore that CFD can be used to design, optimize, and scale-up these processes. 相似文献
948.
Sarti F Barthelmes J Iqbal J Hintzen F Bernkop-Schnürch A 《The Journal of pharmacy and pharmacology》2011,63(3):392-399
Objectives The intestinal stability of perorally administered drugs has so far been determined using simulated intestinal fluid containing porcine pancreatin (SIF/P), as human gastrointestinal fluids are in most cases not available. In this study the metabolism of six low molecular mass drugs in SIF/P was compared with that in freshly collected porcine intestinal juice and on excised porcine intestinal mucosa. Methods The drugs used were oseltamivir, atazanavir, diloxanide, diltiazem, cephalothin and cefoxitin. Metabolism studies were carried out by incubating each drug in the in‐vitro models and by analysing the percentage of unmodified remaining drug at fixed time points. Key findings Three drugs showed higher degradation on porcine mucosa compared with that in SIF/P and for five compounds a significantly higher metabolism in collected porcine intestinal juice versus SIF/P was observed. Metabolism of diloxanide furoate in collected intestinal juice, for example, was 40‐fold higher compared with SIF/P. Moreover, the involvement of different metabolic pathways in porcine mucosa and intestinal juice was observed for cephalothin, being metabolized to desacetylcephalothin and thienyl‐acetylglycine, whereas these metabolites were not found in SIF/P. In addition, diltiazem solution (0.25% m/v) was found to be significantly degraded in intestinal juice whereas its metabolism in SIF/P was negligible. Conclusions These findings demonstrated that the use of SIF/P for evaluation of presystemic drug metabolism could be highly misleading. Incubation of drugs in freshly collected porcine intestinal juice will likely lead to the improvement of the mimicry of body conditions to evaluate presystemic drug metabolism. 相似文献
949.
950.
Gold nanoparticles (AuNPs) are produced for many applications but there is a lack of available data on their skin absorption. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. A physiological solution was used as receiving phase and 0.5 mL (1st exp) and 1.5 mL (2nd exp) of a solution containing 100 mg L?1 of AuNPs (15 and 45 μg cm?2, respectively) was applied as donor phase to the outer surface of the skin for 24 h. Skin absorption was dose dependent. Mean gold content of 214.0 ± 43.7 ng cm?2 and 187.7 ± 50.2 ng cm?2 were found in the receiving solutions of cells where the AuNPs solution was applied in higher concentration on intact skin (8 Franz cells) and on damaged skin (8 Franz cells), respectively. Twenty-four hours gold flux permeation was 7.8 ± 2.0 ng cm?2 h?1 and 7.1 ± 2.5 ng cm?2 h?1 in intact and damaged skin, respectively, with a lag time less than 1 hour. Transmission Electron Microscope analysis on skin samples and chemical analysis using Inductively Coupled Plasma-Mass Spectrometry demonstrated the presence of AuNPs into epidermis and dermis. This study showed that AuNPs are able to penetrate the human skin in an in vitro diffusion cell system. 相似文献