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1.
Rolf Svedjeholm Gabriele Ferrari Farkas Vanky Örjan Friberg Jonas Holm 《Acta anaesthesiologica Scandinavica》2023,67(10):1373-1382
Background
Glutamate plays a key role for post-ischaemic recovery of myocardial metabolism. According to post hoc analyses of the two GLUTAMICS trials, patients without diabetes benefit from glutamate with less myocardial dysfunction after coronary artery bypass surgery (CABG). Copeptin reflects activation of the Arginine Vasopressin system and is a reliable marker of heart failure but available studies in cardiac surgery are limited. We investigated whether glutamate infusion is associated with reduced postoperative rises of plasma Copeptin (p-Copeptin) after CABG.Methods
A prespecified randomised double-blind substudy of GLUTAMICS II. Patients had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥3.0 and underwent CABG ± valve procedure. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h was commenced 10–20 min before the release of the aortic cross-clamp and then continued for another 150 min P-Copeptin was measured preoperatively and postoperatively on day one (POD1) and day three. The primary endpoint was an increase in p-Copeptin from the preoperative level to POD1. Postoperative stroke ≤24 h and mortality ≤30 days were safety outcomes.Results
We included 181 patients of whom 48% had diabetes. The incidence of postoperative mortality ≤30 days (0% vs. 2.1%; p = .50) and stroke ≤24 h (0% vs. 3.2%; p = .25) did not differ between the glutamate group and controls. P-Copeptin increased postoperatively with the highest values recorded on POD1 without significant inter-group differences. Among patients without diabetes, p-Copeptin did not differ preoperatively but postoperative rise from preoperative level to POD1 was significantly reduced in the glutamate group (73 ± 66 vs. 115 ± 102 pmol/L; p = .02). P-Copeptin was significantly lower in the Glutamate group on POD1 (p = .02) and POD 3 (p = .02).Conclusions
Glutamate did not reduce rises of p-Copeptin significantly after moderate to high-risk CABG. However, glutamate was associated with reduced rises of p-Copeptin among patients without diabetes. These results agree with previous observations suggesting that glutamate mitigates myocardial dysfunction after CABG in patients without diabetes. Given the exploratory nature of these findings, they need to be confirmed in future studies. 相似文献2.
Andrea Ferrari MD Daniel Orbach MD Michela Casanova MD Max M. van Noesel MD Pablo Berlanga MD Bernadette Brennan MD Nadege Corradini MD Reineke A. Schoot MD Gema L. Ramirez-Villar MD Lisa Lyngsie Hjalgrim MD Rita Alaggio MD Gabriela Guillen Burrieza MD Akmal Safwat MD Alison L. Cameron MD Rick R. van Rijn MD Veronique Minard-Colin MD Ilaria Zanetti BSc Gianni Bisogno MD Julia C. Chisholm MD Johannes H. M. Merks MD 《Cancer》2023,129(16):2542-2552
Background
Limited data exist on the clinical behavior of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with distant metastases at onset, and a clear standard of care has not yet been defined.Methods
This cohort study reports on pediatric adult-type metastatic NRSTS enrolled in two concurrent prospective European studies, i.e., the randomized BERNIE study and the single-arm MTS 2008 study developed by the European paediatric Soft tissue sarcoma Study Group. Treatment programs were originally designed for patients with metastatic rhabdomyosarcoma, i.e., nine courses of multidrug chemotherapy (with or without bevacizumab in the BERNIE study), followed by 12 cycles of maintenance therapy, whereas radiotherapy and/or surgery (on primary tumor and/or metastases) were delayed until after seven courses of chemotherapy had been administered.Results
The study included 61 patients <21 years old treated from July 2008 to December 2016. The lung was the site of metastases in 75% of the cases. All patients received multi-agent chemotherapy, 44% had local therapy to primary tumor, and 18% had treatment of metastases. Median time to progression/relapse was 6 months. A high rate of tumor progression was observed during the initial part of the chemotherapy program. With a median follow-up of 41.5 months (range, 2–111 months), 3-year event-free survival and overall survival were 15.4% (95% confidence interval [CI], 7.6–25.7) and 34.9% (95% CI, 22.7–47.5), respectively. There were no statistically significant differences in outcome depending on the type of treatment administered.Conclusions
The study confirmed the overall poor outcome for patients with metastatic NRSTS, whose treatment remains a challenge.Plain Language Summary
- Pediatric non-rhabdomyosarcoma soft tissue sarcomas form a heterogeneous group of rare tumors.
- Although recent international studies have defined the standard of care for patients with localized disease, limited data are available on the clinical behavior of patients with distant metastases.
- This study on 61 metastatic cases treated on two prospective European protocols confirms that the chances of survival of such patients are often dismal and a standard treatment is still lacking.
3.
Julie A. Schmidt Georgina K. Fensom Sabina Rinaldi Augustin Scalbert Paul N. Appleby David Achaintre Audrey Gicquiau Marc J. Gunter Pietro Ferrari Rudolf Kaaks Tilman Kühn Heiner Boeing Antonia Trichopoulou Anna Karakatsani Eleni Peppa Domenico Palli Sabina Sieri Rosario Tumino Bas Bueno-de-Mesquita Antonio Agudo Maria-Jose Sánchez María-Dolores Chirlaque Eva Ardanaz Nerea Larrañaga Aurora Perez-Cornago Nada Assi Elio Riboli Konstantinos K. Tsilidis Timothy J. Key Ruth C. Travis 《International journal of cancer. Journal international du cancer》2020,146(3):720-730
Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer. 相似文献
4.
5.
Murat Yücel Erin Oldenhof Serge H. Ahmed David Belin Joel Billieux Henrietta Bowden‐Jones Adrian Carter Samuel R. Chamberlain Luke Clark Jason Connor Mark Daglish Geert Dom Pinhas Dannon Theodora Duka Maria Jose Fernandez‐Serrano Matt Field Ingmar Franken Rita Z. Goldstein Raul Gonzalez Anna E. Goudriaan Jon E. Grant Matthew J. Gullo Robert Hester David C. Hodgins Bernard Le Foll Rico S. C. Lee Anne Lingford‐Hughes Valentina Lorenzetti Scott J. Moeller Marcus R. Munaf Brian Odlaug Marc N. Potenza Rebecca Segrave Zsuzsika Sjoerds Nadia Solowij Wim van den Brink Ruth J. van Holst Valerie Voon Reinout Wiers Leonardo F. Fontenelle Antonio Verdejo‐Garcia 《Addiction (Abingdon, England)》2019,114(6):1095-1109
6.
Olivari Davide De Giorgio Daria Staszewsky Lidia Irene Fumagalli Francesca Boccardo Antonio Novelli Deborah Manfredi Martina Babini Giovanni Luciani Anita Ruggeri Laura Magliocca Aurora Zani Davide Danilo Masson Serge Belloli Angelo Pravettoni Davide Maiocchi Giuseppe Latini Roberto Ristagno Giuseppe 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2022,36(4):727-738
Cardiovascular Drugs and Therapy - Available animal models of acute heart failure (AHF) and their limitations are discussed herein. A novel and preclinically relevant porcine model of decompensated... 相似文献
7.
Alessandro Vairo Matteo Marro Gaetano Maria De Ferrari Mauro Rinaldi Stefano Salizzoni 《Echocardiography (Mount Kisco, N.Y.)》2019,36(11):2090-2093
The NeoChord procedure is an innovative microinvasive, transventricular, beating‐heart chordal replacement technique for patients with severe degenerative mitral valve regurgitation resulting from prolapsed or flail leaflets. Use of three‐dimensional (3D) transoesophageal echocardiographic imaging is crucial to the physician operator for device navigation during the procedure and to assess the functional results of the repair at the end of the procedure. Photo‐realistic, 3D rendering techniques have been recently developed for medical use. Philips TrueVue (Philips Healthcare, Eindhoven, NL) is a photo‐realism technique that employs the use of a virtual light source that simulates the interaction of light on 3‐dimensional surfaces. Use of photo‐realism techniques, in conjunction with 3D echocardiography, improves the visualization of morphological characteristics of the mitral valve before, during, and after beating‐heart mitral valve repair procedures. 相似文献
8.
9.
S. Ghazaleh Dashti Julie A. Simpson Amalia Karahalios Vivian Viallon Margarita Moreno-Betancur Lyle C. Gurrin Robert J. MacInnis Brigid M. Lynch Laura Baglietto Howard A. Morris Marc J. Gunter Pietro Ferrari Roger L. Milne Graham G. Giles Dallas R. English 《International journal of cancer. Journal international du cancer》2020,146(6):1541-1552
Adiposity increases estrogen receptor (ER)-positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex-steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER-positive postmenopausal breast cancer association. We used data from a case–cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER-negative disease or breast cancer diagnosis within the first follow-up year were excluded. We analyzed the study as a cumulative sampling case–control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression-based multiple-mediator approach. For women with body mass index (BMI) >30 kg/m2 compared to women with BMI 18.5–25 kg/m2, the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05–2.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43–2.48). Percentage mediated effect through free estradiol was 72% (IIE-RR 1.56; 95% CI 1.11–2.19). There was no evidence for an indirect effect through insulin (IIE-RR 1.12; 95% CI 0.68–1.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity–breast cancer relationship but does not explain all of the association. 相似文献
10.
Jennifer E. Amengual Jennifer K. Lue Helen Ma Renee Lichtenstein Bijal Shah Serge Cremers Simon Jones Ahmed Sawas 《The oncologist》2021,26(3):184-e366
Lessons Learned
- Oral selective HDAC6 inhibitors could allow for decreased toxicity compared to pan‐class inhibitors, and increased ease of use.
- ACY‐1215 is well tolerated and led to disease stabilization in 50% of patients treated on a twice‐daily dosing schedule.
- Rational drug combinations with ACY‐1215 improve efficacy in patients with lymphoma.
- Biomarkers such as XBP‐1 level or HDAC6‐score may improve patient selection.