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排序方式: 共有4132条查询结果,搜索用时 19 毫秒
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U. Ravens Michael O. Flüß Q. Li Herbert M. Himmel Erich Wettwer Michael Klockow Inge Lues 《Naunyn-Schmiedeberg's archives of pharmacology》1997,355(6):733-742
The thiadiazinone derivative [+]-EMD 60263 ((+)-5-(1-(α-ethylimino-3,4-dimethoxybenzyl)-1,2,3,4- tetrahydroquinoline-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4
-thiadiazine-2-on) is a Ca2+-sensitizing agent with only minor phosphodiesterase inhibitory activity. Our aim was to characterize the inotropic and electrophysiological
effects of [+]-EMD 60263 and its enantiomer [-]-EMD 60264 in several cardiac muscle preparations. The Ca2+-sensitizing activity resided in the [+]-enantiomer only. [+]-EMD 60263 (3 μM) shifted the EC50 of Ca2+ for contractile activation of skinned fibers of pig heart from 2.41 μM to 0.73 μM, whereas [-]-EMD 60264 (30 μM) was ineffective.
In Langendorff-perfused guinea pig hearts, [+]-EMD 60263 and [-]-EMD 60264 induced concentration-dependent positive and negative
inotropic effects, respectively; both enantiomers reduced spontaneous heart rate but did not influence perfusion pressure.
The maximum increase in force of human atrial trabeculae was 35 % of pre-drug control with [+]-EMD 60263 in comparison to
113 % with forskolin. In guinea-pig papillary muscles, [+]-EMD 60263 and [-]-EMD 60264 had opposite inotropic responses, however,
both agents similarly prolonged action potential duration. Both enantiomers concentration-dependently blocked the rapidly
activating component IKr of the delayed rectifier in guinea-pig myocytes. The block saturated at potentials positive to +30 mV, closely resembling
the effects of the antiarrhythmic agent E-4031 which had been originally used to define IKr. It is concluded, that the positive inotropic action of [+]-EMD 60263 can be explained by prevalence of the Ca2+-sensitizing effect. The accompanying prolongation in action potential duration is caused by block of the IKr component of the delayed rectifier. While the inotropic effects are stereoselective, most of the electrophysiological actions
are clearly independent of sterical configuration. The combination of Ca2+-sensitizing with class-III antiarrhythmic action may provide an interesting pharmacological profile of potential therapeutic
use.
Received: 7 January 1997 / Accepted: 25 February 1997 相似文献
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Monitoring left ventricular dilation in mice with PET. 总被引:3,自引:0,他引:3
Lars Stegger Klaus P Sch?fers Ulrich Fl?gel Lefteris Livieratos Sven Hermann Christoph Jacoby Petra Keul Edward M Conway Otmar Schober Jürgen Schrader Bodo Levkau Michael Sch?fers 《Journal of nuclear medicine》2005,46(9):1516-1521
Molecular imaging by small-animal PET is an important noninvasive means to phenotype transgenic mouse models in vivo. When investigating pathologies of the left ventricular (LV) myocardium, the serial assessment of LV volumes is important. By this, the presence of LV dilation as a sign of developing heart failure can be detected. Whereas PET is usually used to derive biochemical and molecular information, functional parameters such as ventricular volumes are generally measured using echocardiography or MRI. In this study, a novel method to monitor LV dilation in mice with PET is presented and evaluated using cardiac MRI. METHODS: A semiautomatic 3-dimensional algorithm was used to delineate the LV myocardial wall on static PET images depicting myocardial glucose metabolism ((18)F-FDG PET) for 20 mice: 10 wild-type and 10 genetically modified littermates designed to develop a dilative cardiomyopathy phenotype (cardiomyocyte-specific knockout of survivin). The volume enclosed by the 3-dimensional midmyocardial contour was calculated as a measure for LV volume for each mouse. Data were compared with ventricular volumes measured by MRI in the same animals. RESULTS: LV volumes obtained by PET and MRI correlated well (R = 0.89) for hearts with small and large left ventricles. In accordance with the hypothesis, the LV volumes were increased significantly for transgenic mice examined at an older age compared with those examined at a younger age (MRI: 160.5 +/- 25.7 microL vs. 114.7 +/- 15.2 microL [P = 0.012]; PET: 129.3 +/- 15.3 microL vs. 73.8 +/- 15.0 microL [P < 0.001], all values shown as mean +/- SD; for MRI, mean of end-diastolic and end-systolic volumes are given), whereas they did not for their wild-type littermates (MRI: 106.2 +/- 12.3 microL vs. 94.7 +/- 14.6 microL [P = 0.214]; PET: 82.6 +/- 20.9 microL vs. 65.0 +/- 16.9 microL [P = 0.185]). CONCLUSION: Evaluation and quantitation of LV dilation in both control and cardiomyopathic mice can be reliably and serially performed using small-animal PET and (18)F-FDG, yielding useful functional information in addition to metabolic data. 相似文献
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Aldo Cunha Medeiros Irami Araújo Filho Vítor Brasil Medeiros Laíza Araújo Mohana Pinheiro Flávio Henrique Miranda Araújo Freire Italo Medeiros Azevedo José Brand?o-Neto 《Journal of investigative surgery》2007,20(1):41-48
After total gastrectomy, the ileocecal graft may act as a reservoir and protect against reflux but give rise to transposition of the ileum and cause possible changes in bile acid metabolism and nutrition. This study compared the ileocecal graft and jejunal pouch. Male Wistar rats weighing 265 +/- 22 g were submitted to sham operation (S), ileocecal interposition graft (IIG), and jejunal pouch interposition graft (JP) after total gastrectomy. Eight weeks later, the esophagus was examined for evidence of esophagitis. Nutritional biochemistry and weight profile were documented preoperatively and 8 weeks after surgery. The oral glucose tolerance test was performed. Thirty-three rats were operated on and 30 survived for 8 weeks. Esophagitis occurred in seven JP rats. Body weight was significantly higher in IIG than in JP rats (p < .05). Normal glucose tolerance to intragastric glucose load was observed in sham and operated rats. JP rats had a significant decrease in serum albumin, glucose, transferrin, hemoglobin, iron, folate, and calcium, compared to sham (p < .05). Cobalamine was significantly lower in IIG rats than in JP rats (p < .05). In the IIG and JP groups, serum/hepatic total bile acid did not differ significantly from preoperative and sham values. In conclusion, the IIG interposition graft in rats prevented esophagitis, preserved nutrition, and did not interfere with enterohepatic total bile acid circulation. 相似文献
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Aureo L DePaula Antonio L V Macedo Claudio R Cernea Vladimir Schraibman Jacques Pinus José R Milanez José E Succi Flávio C Hojaij Dorival de Carlucci Sunao Nishio 《Otolaryngology--head and neck surgery》2006,135(5):710-713
BACKGROUND: Gastric pull-up is a useful method for reconstruction of the upper digestive tract, with considerable morbidity/mortality, especially in esophageal cancers (EC). OBJECTIVE: To analyze the experience of a multidisciplinary team with a laparoscopic gastric pull-up (LGPU) method, with or without thoracoscopy, in a series of 120 patients with EC. STUDY DESIGN: Retrospective. PATIENTS AND METHODS: From 1992 to 2004, 120 EC [cervical/cervicothoracic (3.0%), middle third (15.0%), and inferior third (82.0%)]. Most were squamous cell carcinomas (47.0%) and adenocarcinomas (34.0%). Stomach was dissected and mobilized exclusively by laparoscopy. Occasionally, laparoscopic approach was extended cranially, until connecting with cervical dissection. In other cases, dissection of thoracic esophagus was accomplished through a thoracoscopic approach. RESULTS: Eighty-one patients (68.0%) had LGPU; 39 (32.0%) needed thoracoscopy. Mortality was 5.9%. Complications were fistula (10.0%) and pneumonia (10.0%). All fistulae closed spontaneously; 89.2% of patients could swallow a normal oral diet. CONCLUSION: Low morbidity/mortality of LGPU for EC compared favorably with conventional techniques. 相似文献