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排序方式: 共有2287条查询结果,搜索用时 15 毫秒
61.
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Fraysse B Weinberger F Bardswell SC Cuello F Vignier N Geertz B Starbatty J Krämer E Coirault C Eschenhagen T Kentish JC Avkiran M Carrier L 《Journal of molecular and cellular cardiology》2012,52(6):1299-1307
Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in MYBPC3 encoding cardiac myosin-binding protein C (cMyBP-C). The mechanisms leading from gene mutations to the HCM phenotype remain incompletely understood, partially because current mouse models of HCM do not faithfully reflect the human situation and early hypertrophy confounds the interpretation of functional alterations. The goal of this study was to evaluate whether myofilament Ca(2+) sensitization and diastolic dysfunction are associated or precede the development of left ventricular hypertrophy (LVH) in HCM. We evaluated the function of skinned and intact cardiac myocytes, as well as the intact heart in a recently developed Mybpc3-targeted knock-in mouse model carrying a point mutation frequently associated with HCM. Compared to wild-type, 10-week old homozygous knock-in mice exhibited i) higher myofilament Ca(2+) sensitivity in skinned ventricular trabeculae, ii) lower diastolic sarcomere length, and faster Ca(2+) transient decay in intact myocytes, and iii) LVH, reduced fractional shortening, lower E/A and E'/A', and higher E/E' ratios by echocardiography and Doppler analysis, suggesting systolic and diastolic dysfunction. In contrast, heterozygous knock-in mice, which mimic the human HCM situation, did not exhibit LVH or systolic dysfunction, but exhibited higher myofilament Ca(2+) sensitivity, faster Ca(2+) transient decay, and diastolic dysfunction. These data demonstrate that myofilament Ca(2+) sensitization and diastolic dysfunction are early phenotypic consequences of Mybpc3 mutations independent of LVH. The accelerated Ca(2+) transients point to compensatory mechanisms directed towards normalization of relaxation. We propose that HCM is a model for diastolic heart failure and this mouse model could be valuable in studying mechanisms and treatment modalities. 相似文献
63.
Hedsund C Gregersen T Joensson IM Olesen HV Krogh K 《Scandinavian journal of gastroenterology》2012,(47):920-926
Abstract Objective. Patients with cystic fibrosis (CF) often suffer from gastrointestinal (GI) dysfunction including obstructive symptoms, malabsorption and pain, but the underlying pathophysiology remains obscure. Aim. To compare GI motility and transit times in CF patients and healthy controls. Material and methods. Ten CF patients (five women, median age 23) with pancreatic insufficiency were studied. Total gastrointestinal transit time (GITT) and segmental colonic transit times (SCTT) were assessed by radiopaque markers. Gastric emptying and small intestinal transit were evaluated using the magnet-based motility tracking system (MTS-1). With each method patients were compared with 16 healthy controls. Results. Basic contraction frequencies of the stomach and small intestine were normal, but the pill reached the cecum after 7 h in only 20% of CF patients while in 88% of controls (p = 0.001). Paradoxically, velocity of the magnetic pill through the upper small intestine tended to be faster in CF patients (median 1.1 cm/min, range 0.7-1.7) compared with controls (median 1.0 cm/min, range 0.6-1.7) (p = 0.09). No statistically significant differences were found in median gastric emptying time (CF: 58 min, range 6-107 vs. healthy: 41 min, range 4-125 (p = 0.24)), GITT (CF: 2 days, range 0.5-3.3 vs. healthy: 1.5 days, range 0.7-2.5 (p = 0.10)), right SCTT (CF: 0.5 day, range 0-1.1 vs. healthy: 0.4 day, range 0-1.0 (p = 0.85)), or left SCTT (CF: 1.0 day, range 0-2.2 vs. healthy 0.6 day, range 0.2-1.2 (p = 0.10)). Conclusions. In spite of normal contraction patterns, overall passage through the small intestine is significantly delayed in CF patients while upper small intestinal transit may be abnormally fast. 相似文献
64.
Jönsson F Mancardi DA Zhao W Kita Y Iannascoli B Khun H van Rooijen N Shimizu T Schwartz LB Daëron M Bruhns P 《Blood》2012,119(11):2533-2544
IgE and IgE receptors (FcεRI) are well-known inducers of allergy. We recently found in mice that active systemic anaphylaxis depends on IgG and IgG receptors (FcγRIIIA and FcγRIV) expressed by neutrophils, rather than on IgE and FcεRI expressed by mast cells and basophils. In humans, neutrophils, mast cells, basophils, and eosinophils do not express FcγRIIIA or FcγRIV, but FcγRIIA. We therefore investigated the possible role of FcγRIIA in allergy by generating novel FcγRIIA-transgenic mice, in which various models of allergic reactions induced by IgG could be studied. In mice, FcγRIIA was sufficient to trigger active and passive anaphylaxis, and airway inflammation in vivo. Blocking FcγRIIA in vivo abolished these reactions. We identified mast cells to be responsible for FcγRIIA-dependent passive cutaneous anaphylaxis, and monocytes/macrophages and neutrophils to be responsible for FcγRIIA-dependent passive systemic anaphylaxis. Supporting these findings, human mast cells, monocytes and neutrophils produced anaphylactogenic mediators after FcγRIIA engagement. IgG and FcγRIIA may therefore contribute to allergic and anaphylactic reactions in humans. 相似文献
65.
N. Japaridze M. Siniatchkin M. Muthuraman J. Raethjen U. Stephani PD Dr. F. Moeller 《Zeitschrift für Epileptologie》2013,26(1):19-24
Electric source imaging allows localization of sources in the brain underlying frequency-associated EEG patterns detected on the scalp EEG. New algorithms have substantially improved the localization power of the EEG. Dynamic imaging of coherent sources (DICS) is one of these solutions. This algorithm uses a spatial filter to map power and coherence estimates of oscillatory brain activity. In this focus article, we explain the DICS method and summarize studies representing the ability of DICS to detect cortical and subcortical electric sources and neuronal networks associated with absence seizures, photoparoxysmal responses and hypsarrhythmia. By applying renormalized partial directed coherence (RPDC), the information flow between 2 sources can be described, which contributes to a better understanding of networks underlying different forms of epilepsy. 相似文献
66.
Verena Tenten Sylvia Menzel Uta Kunter Eva-Maria Sicking Claudia R. C. van Roeyen Silja K. Sanden Michaela Kaldenbach Peter Boor Astrid Fuss Sandra Uhlig Regina Lanzmich Brigith Willemsen Henry Dijkman Martin Grepl Klemens Wild Wilhelm Kriz Bart Smeets Jürgen Floege Marcus J. Moeller 《Journal of the American Society of Nephrology : JASN》2013,24(12):1966-1980
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Friederike Weigel Anja Lemke Burkhard Tönshoff Lars Pape Henry Fehrenbach Michael Henn Bernd Hoppe Therese Jungraithmayr Martin Konrad Guido Laube Martin Pohl Tomáš Seeman Hagen Staude Markus J. Kemper Ulrike John 《Pediatric nephrology (Berlin, Germany)》2016,31(6):1021-1028