全文获取类型
收费全文 | 2861篇 |
免费 | 195篇 |
国内免费 | 11篇 |
专业分类
耳鼻咽喉 | 90篇 |
儿科学 | 40篇 |
妇产科学 | 30篇 |
基础医学 | 487篇 |
口腔科学 | 40篇 |
临床医学 | 282篇 |
内科学 | 580篇 |
皮肤病学 | 49篇 |
神经病学 | 358篇 |
特种医学 | 152篇 |
外科学 | 395篇 |
综合类 | 17篇 |
预防医学 | 95篇 |
眼科学 | 59篇 |
药学 | 186篇 |
肿瘤学 | 207篇 |
出版年
2023年 | 23篇 |
2022年 | 35篇 |
2021年 | 55篇 |
2020年 | 49篇 |
2019年 | 51篇 |
2018年 | 75篇 |
2017年 | 54篇 |
2016年 | 99篇 |
2015年 | 84篇 |
2014年 | 93篇 |
2013年 | 124篇 |
2012年 | 227篇 |
2011年 | 245篇 |
2010年 | 164篇 |
2009年 | 128篇 |
2008年 | 212篇 |
2007年 | 229篇 |
2006年 | 196篇 |
2005年 | 193篇 |
2004年 | 176篇 |
2003年 | 159篇 |
2002年 | 130篇 |
2001年 | 44篇 |
2000年 | 31篇 |
1999年 | 26篇 |
1998年 | 19篇 |
1997年 | 24篇 |
1996年 | 11篇 |
1995年 | 7篇 |
1994年 | 2篇 |
1993年 | 13篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1989年 | 9篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 14篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1974年 | 5篇 |
1961年 | 3篇 |
1943年 | 1篇 |
排序方式: 共有3067条查询结果,搜索用时 31 毫秒
71.
72.
Measuring quality of life in patients with head and neck cancer: Update of the EORTC QLQ‐H&N Module,Phase III 下载免费PDF全文
Susanne Singer Cludia Araújo Juan Ignacio Arraras Ingo Baumann Andreas Boehm Bente Brokstad Herlofson Joaquim Castro Silva Wei‐Chu Chie Sheila Fisher Orlando GuntinasLichius Eva Hammerlid María Elisa Irarrzaval Marianne Jensen Hjermstad Kenneth Jensen Naomi Kiyota Lisa Licitra Ourania NicolatouGalitis Monica Pinto Marcos Santos Claudia Schmalz Allen C. Sherman Iwona M. Tomaszewska Irma Verdonck de Leeuw Noam Yarom Paola Zotti Dirk Hofmeister 《Head & neck》2015,37(9):1358-1367
73.
Is there a Rationale for Autologous Breast Reconstruction in Older Patients? A Retrospective Single Center Analysis of Quality of life,Complications and Comorbidities after DIEP or ms‐TRAM Flap Using the BREAST‐Q 下载免费PDF全文
Ingo Ludolph MD Raymund E. Horch MD Marina Harlander MD Andreas Arkudas MD Alexander D. Bach MD Ulrich Kneser MD Marweh Schmitz MD Christian D. Taeger MD Justus P. Beier MD 《The breast journal》2015,21(6):588-595
Autologous breast reconstruction with the deep inferior epigastric perforator (DIEP) or muscle‐sparing transverse rectus abdominis myocutaneous (ms‐TRAM) flap is a common method in the majority of patients after mastectomy. Because of an increased perioperative risk profile the benefit in older patients is questionable. To assess the postoperative quality of life and peri‐ and post‐operative complications of older compared to younger patients is the aim of this retrospective study. In a retrospective analysis 39 older (i.e. >60 years) and 140 younger patients (i.e. <60 years) with autologous breast reconstruction in the Department of Plastic Surgery at the University Hospital of Erlangen‐Nuernberg were surveyed at least 6 month postoperative using the BREAST‐Q questionnaire. Correlations were generated between comorbidities and complications. Significant differences were observed regarding hospitalization, pre‐existing diseases and the choice of DIEP versus ms‐TRAM flaps. Parameters such as major and minor complications, bulging or hernia and risk factors (e.g. smoking or obesity) showed no significant differences. The results of the questionnaire parameters showed no significant difference between both groups, revealing high satisfaction with the aesthetic result and an improvement in quality of life independent of age. Autologous breast reconstruction after mastectomy generates a gain in quality of life and shows a good to excellent overall satisfaction in older as well as younger patients. Despite a longer hospitalization and a different risk profile there were no significant differences regarding minor and major complications in the postoperative course. Hence autologous breast reconstruction for older patients is justified and should be taken into consideration. 相似文献
74.
Ingo Helbig Marielle E M Swinkels Emmelien Aten Almuth Caliebe Ruben van 't Slot Rainer Boor Sarah von Spiczak Hiltrud Muhle Johanna A J?hn Ellen van Binsbergen Onno van Nieuwenhuizen Floor E Jansen Kees P J Braun Gerrit-Jan de Haan Niels Tommerup Ulrich Stephani Helle Hjalgrim Martin Poot Dick Lindhout Eva H Brilstra Rikke S M?ller Bobby PC Koeleman 《European journal of human genetics : EJHG》2014,22(7):896-901
A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies. 相似文献
75.
Marc Luginbühl Wolfgang Weinmann Ingo Butzke Philippe Pfeifer 《Drug testing and analysis》2019,11(6):859-869
Direct and indirect biomarkers are widely applied for the determination of alcohol consumption. They help to assess past or present alcohol consumption. Depending on the window of detection and sensitivity of the investigated marker, punctual alcohol consumption may remain undetected. In this study, different sampling strategies for the intermediary long‐term marker phosphatidylethanol (PEth) are evaluated and compared to the determination of the short‐term markers ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine. Samples from 19 patients undergoing alcohol use disorder treatment were collected during the withdrawal treatment and successive rehabilitation (33 ± 26 days (range: 3–74 days)). With liquid chromatography–tandem mass spectrometry (LC–MS/MS) EtG and EtS in urine, PEth in blood, PEth in dried blood spot (DBS) from venous blood, and PEth in DBS from capillary blood were quantified and compared. The use of volumetric capillary DBS, prepared from 20 μL of blood, provided the same results as the use of venous DBS (95% ± 10%, R2 0.9899 for PEth 16:0/18:1). Capillary DBS sampling has the advantage that it can be performed without venipuncture. The use of PEth in DBS proved to prevent post‐sampling degradation, providing a longer detection in comparison to PEth in liquid blood, which only showed 67% ± 24% of the PEth DBS 16:0/18:1 concentration. When compared with EtG and EtS in urine, PEth monitoring proved to be advantageous for the detection of relapse situations, as the accumulation of PEth in blood prolongs the detectability. In conclusion, volumetric capillary DBS sampling for PEth is a simple and useful tool for compliance monitoring, and avoids hematocrit issues. 相似文献
76.
Local proliferation of macrophages in adipose tissue during obesity-induced inflammation 总被引:1,自引:0,他引:1
Julia Haase Ulrike Weyer Kerstin Immig Nora Klöting Matthias Blüher Jens Eilers Ingo Bechmann Martin Gericke 《Diabetologia》2014,57(3):562-571
Aims/hypothesis
Obesity is frequently associated with low-grade inflammation of adipose tissue (AT), and the increase in adipose tissue macrophages (ATMs) is linked to an increased risk of type 2 diabetes. Macrophages have been regarded as post-mitotic, but recent observations have challenged this view. In this study, we tested the hypothesis that macrophages proliferate within AT in diet-induced obesity in mice and humans.Methods
We studied the expression of proliferation markers by immunofluorescence, PCR and flow cytometry in three different models of mouse obesity as well as in humans (n?=?239). The cell fate of dividing macrophages was assessed by live imaging of AT explants.Results
We show that ATMs undergo mitosis within AT, predominantly within crown-like structures (CLS). We found a time-dependent increase in ATM proliferation when mice were fed a high-fat diet. Upregulation of CD206 and CD301 in proliferating ATMs indicated preferential M2 polarisation. Live imaging within AT explants from mice revealed that macrophages emigrate out of the CLS to become resident in the interstitium. In humans, we confirmed the increased expression of proliferation markers of CD68+ macrophages in CLS and demonstrated a higher mRNA expression of the proliferation marker Ki67 in AT from obese patients.Conclusions/interpretation
Local proliferation contributes to the increase in M2 macrophages in AT. Our data confirm CLS as the primary site of proliferation and a new source of ATMs and support a model of different recruitment mechanisms for classically activated (M1) and alternatively activated (M2) macrophages in obesity. 相似文献77.
78.
Svenja Sydor Paul Manka Lea van Buren Sarah Theurer Suzan Schwertheim Jan Best Janette Heegsma Ali Saeed Diana Vetter Martin Schlattjan Anna Dittrich Maria I. Fiel Hideo A. Baba Alexander Dechêne Francisco J. Cubero Guido Gerken Ali Canbay Han Moshage Scott L. Friedman Klaas Nico Faber Lars P. Bechmann 《Liver international》2020,40(9):2172-2181
79.
Sabine Zollner Elmar Raquet Philipp Claar Jochen Müller-Cohrs Hubert J. Metzner Thomas Weimer Ingo Pragst Gerhard Dickneite Stefan Schulte 《Thrombosis research》2014
Introduction
rVIII-SingleChain (CSL627), a novel recombinant coagulation factor VIII (FVIII), is under investigation in a phase I/III clinical programme (AFFINITY) for the treatment of haemophilia A. Non-clinical studies were conducted to investigate the pharmacokinetic/pharmacodynamic profile of rVIII-SingleChain in comparison with full-length recombinant FVIII.Materials and Methods
Binding affinity of rVIII-SingleChain for von Willebrand factor was investigated by surface plasmon resonance analysis. The pharmacokinetic profile of rVIII-SingleChain was compared with a marketed full-length recombinant FVIII concentrate (Advate®) in haemophilia A mice, von Willebrand factor knock-out mice, Crl:CD (SD) rats, rabbits and cynomolgus monkeys. Systemic FVIII activity or antigen levels were recorded. Procoagulant activity was measured in an FeCl3-induced arterial occlusion model and by recording thrombin generation activity (ex vivo) after administration of 200–250 IU/kg rVIII-SingleChain or full-length FVIII to haemophilia A mice.Results
rVIII-SingleChain displayed a high affinity for von Willebrand factor (KD = 44 pM vs. 139 pM for full-length recombinant FVIII). In all animal species tested, rVIII-SingleChain had more favourable pharmacokinetic properties than full-length recombinant FVIII: clearance was decreased and area under the curve and terminal half-life were enhanced vs. full-length recombinant FVIII, while in vivo recovery and volume of distribution were equivalent. rVIII-SingleChain showed a prolonged thrombin generation potential and prolonged procoagulant activity vs. full-length recombinant FVIII in an FeCl3-induced arterial occlusion model.Conclusions
rVIII-SingleChain had a higher affinity for von Willebrand factor than full-length recombinant FVIII and displayed favourable pharmacokinetic/pharmacodynamic properties in non-clinical models. 相似文献80.
Mergenthaler P Kahl A Kamitz A van Laak V Stohlmann K Thomsen S Klawitter H Przesdzing I Neeb L Freyer D Priller J Collins TJ Megow D Dirnagl U Andrews DW Meisel A 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(5):1518-1523
The metabolic state of a cell is a key determinant in the decision to live and proliferate or to die. Consequently, balanced energy metabolism and the regulation of apoptosis are critical for the development and maintenance of differentiated organisms. Hypoxia occurs physiologically during development or exercise and pathologically in vascular disease, tumorigenesis, and inflammation, interfering with homeostatic metabolism. Here, we show that the hypoxia-inducible factor (HIF)-1-regulated glycolytic enzyme hexokinase II (HKII) acts as a molecular switch that determines cellular fate by regulating both cytoprotection and induction of apoptosis based on the metabolic state. We provide evidence for a direct molecular interactor of HKII and show that, together with phosphoprotein enriched in astrocytes (PEA15), HKII inhibits apoptosis after hypoxia. In contrast, HKII accelerates apoptosis in the absence of PEA15 and under glucose deprivation. HKII both protects cells from death during hypoxia and functions as a sensor of glucose availability during normoxia, inducing apoptosis in response to glucose depletion. Thus, HKII-mediated apoptosis may represent an evolutionarily conserved altruistic mechanism to eliminate cells during metabolic stress to the advantage of a multicellular organism. 相似文献