全文获取类型
收费全文 | 4436篇 |
免费 | 294篇 |
国内免费 | 12篇 |
专业分类
耳鼻咽喉 | 114篇 |
儿科学 | 264篇 |
妇产科学 | 157篇 |
基础医学 | 455篇 |
口腔科学 | 130篇 |
临床医学 | 479篇 |
内科学 | 812篇 |
皮肤病学 | 101篇 |
神经病学 | 355篇 |
特种医学 | 174篇 |
外科学 | 661篇 |
综合类 | 52篇 |
一般理论 | 1篇 |
预防医学 | 366篇 |
眼科学 | 151篇 |
药学 | 222篇 |
中国医学 | 2篇 |
肿瘤学 | 246篇 |
出版年
2024年 | 4篇 |
2023年 | 45篇 |
2022年 | 80篇 |
2021年 | 166篇 |
2020年 | 85篇 |
2019年 | 160篇 |
2018年 | 165篇 |
2017年 | 145篇 |
2016年 | 145篇 |
2015年 | 183篇 |
2014年 | 218篇 |
2013年 | 313篇 |
2012年 | 381篇 |
2011年 | 350篇 |
2010年 | 220篇 |
2009年 | 147篇 |
2008年 | 308篇 |
2007年 | 295篇 |
2006年 | 249篇 |
2005年 | 264篇 |
2004年 | 206篇 |
2003年 | 171篇 |
2002年 | 144篇 |
2001年 | 41篇 |
2000年 | 37篇 |
1999年 | 39篇 |
1998年 | 13篇 |
1997年 | 13篇 |
1996年 | 14篇 |
1995年 | 10篇 |
1994年 | 6篇 |
1993年 | 9篇 |
1992年 | 16篇 |
1991年 | 12篇 |
1990年 | 9篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1978年 | 6篇 |
1977年 | 4篇 |
1968年 | 4篇 |
1966年 | 4篇 |
排序方式: 共有4742条查询结果,搜索用时 0 毫秒
101.
Altan N Chen Y Schindler M Simon SM 《Proceedings of the National Academy of Sciences of the United States of America》1999,96(8):4432-4437
Tamoxifen has been reported to have numerous physiological effects that are independent of the estrogen receptor, including sensitization of resistant tumor cells to many chemotherapeutic agents. Drug-resistant cells sequester weak base chemotherapeutics in acidic organelles away from their sites of action in the cytosol and nucleus. This work reports that tamoxifen causes redistribution of weak base chemotherapeutics from acidic organelles to the nucleus in drug-resistant cells. Agents that disrupt organelle acidification (e.g., monensin, bafilomycin A1) cause a similar redistribution. Measurement of cellular pH in several cell lines reveals that tamoxifen inhibits acidification of endosomes and lysosomes without affecting cytoplasmic pH. Similar to monensin, tamoxifen decreased the rate of vesicular transport though the recycling and secretory pathways. Organellar acidification is required for many cellular functions, and its disruption could account for many of the side effects of tamoxifen. 相似文献
102.
Erbay AR Turhan H Senen K Yetkin F Ayaz S Kara F Buyukasik NS Yetkin E 《Coronary artery disease》2004,15(2):107-110
OBJECTIVES: The aim of this study was to investigate the association between left ventricular thrombus formation and natural anticoagulant systems including the protein C, protein S and antithrombin in patients with dilated cardiomyopathy. MATERIALS AND METHODS: Sixty patients with dilated cardiomyopathy who met the inclusion criteria were included in the study. Patients were divided into two groups: group I consisted of 22 patients with left ventricular thrombus and group II consisted of 38 patients without left ventricular thrombus. Our main inclusion criteria were ejection fraction = 35% and left ventricular end-diastolic diameter >/= 6.0 cm. These two groups were compared for clinical and hematologic parameters (activated protein C resistance, protein S and antithrombin). RESULTS: There were no statistically significant differences between patients with or without left ventricular thrombi with respect to left ventricular end-diastolic and end-systolic dimensions, ejection fraction, fractional shortening and left atrial diameter. There were no statistically significant differences between patients with and without left ventricular thrombus with respect to platelet count (252 +/- 64/mm3 x 10(3) compared with 260 +/- 74/mm3 x 10(3) respectively, P=0.68), prothrombin time (12.94 +/- 1.9 s compared with 12.86 +/- 1.3 s respectively, P=0.82), activated partial thromboplastin time (32 +/- 5 compared with 30 +/- 4 s respectively, P=0.32) and fibrinogen levels (36 +/- 9 mg/dl compared with 34 +/- 8 mg/dl respectively, P=0.41). None of the patients had protein S and antithrombin deficiency. Activated protein C resistance was found in 12 patients (12 out of 22, 54%) in group I and four patients (four out of 38, 9.5%) in group II (P < 0.01). It was also shown to be an independent predictor of left ventricular thrombus (P < 0.05). CONCLUSION: Activated protein C resistance is found to be an independent predictor of left ventricular thrombus in patients with dilated cardiomyopathy who have ejection fractions less then 35% and left ventricular end-diastolic dimensions > 6.0 cm. 相似文献
103.
104.
The cardiac myofilament protein troponin I (cTnI) is phosphorylated by protein kinase C (PKC), a family of serine/threonine kinases activated within heart muscle by a variety of agonists. cTnI is also a substrate for cAMP-dependent protein kinase (PKA) activated during beta-adrenergic signaling. To investigate the role of cTnI phosphorylation in contractile regulation by these pathways, we generated transgenic mice harboring a mutated cTnI protein lacking phosphorylation sites for PKC (serine(43/45) and threonine(144) mutated to alanine) and for PKA (serine(23/24) mutated to alanine). Transgenic mice were interbred with cTnI-knockout mice to ensure the absence of endogenous phosphorylatable cTnI. Here, we report that regulation of myocyte twitch kinetics by beta-stimulation and by endothelin-1 was altered in myocytes containing mutant cTnI. In wild-type myocytes, the beta-agonist isoproterenol decreased twitch duration and relaxation time constant (tau) by 37% to 44%. These lusitropic effects of isoproterenol were reduced by about half in nonphosphorylatable cTnI mutant myocytes and were absent in cTnI mutants also lacking phospholamban (generated by crossing cTnI mutants with phospholamban-knockout mice). These observations are consistent with important roles for both cTnI and phospholamban phosphorylation in accelerating relaxation after beta-adrenergic stimulation. In contrast, endothelin-1 increased twitch duration by 32% and increased tau by 58%. These endothelin-1 effects were substantially blunted in nonphosphorylatable cTnI myocytes, indicating that PKC phosphorylation of cTnI slows cardiac relaxation and increases twitch duration. We propose that beta-agonists and endothelin-1 regulate cardiac twitch dynamics in opposite directions in part through phosphorylation of the myofilament protein cTnI on distinct sites. 相似文献
105.
106.
Nazl?han Günal Nazl? Kara Nilgün Çakar Hulusi Koçak Öz Kahramanyol Ergun Çetinkaya 《International journal of cardiology》1997,60(3):17-262
In this report, we evaluated the cardiac findings of 15 children with polyarteritis nodosa. The age range of the patients was 4–14 years; with a mean of 10 years. All have had systemic involvement of the disease. The most common findings in cardiac evaluation were diminished left ventricular systolic functions and mild mitral and/or tricuspid valve regurgitation. One patient had pericardial thickening with no effusion. One had sinus tachycardia. There were no signs of myocardial infarction or ischemia clinically or electrocardiographically. In conclusion, we did not find cardiac complications, such as pericarditis or myocardial infarction, to be as frequent as in previous reports. However, even in asymptomatic patients, systolic dysfunction or valvular involvement were common findings in patients with polyarteritis nodosa, which were not reported previously. These findings may be due to the histological changes of the myocardium or atrioventricular valves. Although these were not severe and fatal lesions, long-term follow-up of these patients with echocardiography may help to determine the course of cardiac involvement. 相似文献
107.
Alain P. Gobert Olivier Boutaud Mohammad Asim Irene A. Zagol-Ikapitte Alberto G. Delgado Yvonne L. Latour Jordan L. Finley Kshipra Singh Thomas G. Verriere Margaret M. Allaman Daniel P. Barry Kara M. McNamara Johanna C. Sierra Venkataraman Amarnath Mohammed N. Tantawy Diane Bimczok M. Blanca Piazuelo M. Kay Washington Keith T. Wilson 《Gastroenterology》2021,160(4):1256-1268.e9
- Download : Download high-res image (348KB)
- Download : Download full-size image
108.
Beta3 integrin deficiency promotes atherosclerosis and pulmonary inflammation in high-fat-fed,hyperlipidemic mice
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Weng S Zemany L Standley KN Novack DV La Regina M Bernal-Mizrachi C Coleman T Semenkovich CF 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(11):6730-6735
Hyperlipidemia promotes the chronic inflammatory disease atherosclerosis through poorly understood mechanisms. Atherogenic lipoproteins activate platelets, but it is unknown whether platelets contribute to early inflammatory atherosclerotic lesions. To address the role of platelet aggregation in diet-induced vascular disease, we studied beta3 integrin-deficient mice (lacking platelet integrin alphaIIbbeta3 and the widely expressed nonplatelet integrin alphavbeta3) in two models of atherosclerosis, apolipoprotein E (apoE)-null and low-density lipoprotein receptor (LDLR)-null mice. Unexpectedly, a high-fat, Western-type (but not a low-fat) diet caused death in two-thirds of the beta3-/-apoE-/- and half of the beta3-/-LDLR-/- mice due to noninfectious pneumonitis. In animals from both models surviving high-fat feeding, pneumonitis was absent, but aortic atherosclerosis was 2- to 6-fold greater in beta3-/- compared with beta+/+ littermates. Expression of CD36, CD40L, and CD40 was increased in lungs of beta3-/-LDLR-/- mice. Each was also increased in smooth muscle cells cultured from beta3-deficient mice and suppressed by retroviral reconstitution of beta3. These data show that the platelet defect caused by alphaIIbbeta3 deficiency does not impair atherosclerotic lesion initiation. They also suggest that alphavbeta3 has a suppressive effect on inflammation, the loss of which induces atherogenic mediators that are amplified by diet-induced hyperlipidemia. 相似文献
109.
Osteoporosis is a multifactorial disease in which genetic determinants are modulated by hormonal, environmental and nutritional factors. The balance between bone resorption and bone formation seems to be regulated by a variety of growth factors and cytokines. An important clinical risk factor in the pathogenesis of osteoporosis is the presence of genetic polymorphisms in susceptibility genes. In this study, we investigated the association between osteoporosis and interleukin 10 (IL-10) −597 C>A and transforming growth factor β1 (TGF-β1) T869C (also named Leu10>Pro) polymorphisms in Turkish postmenopausal women. Genomic DNA obtained from 255 individuals (152 osteoporotic and 103 healthy controls). The DNA sample was isolated from peripheral bloods by salting-out method and analyzed by the techniques of PCR-RFLP. Genotype and allele frequencies were calculated and data were analyzed using the χ2 test. We found a statistically significant difference between the groups with respect to IL-10 genotype distribution (p = 0.001) and allele frequencies (p < 0.0002). However, we did not found any difference between the groups with regarding TGF-β1 genotype distribution and allele frequencies (p > 0.05). In the combined genotype analysis, IL-10/TGF-β1 CCCC combine genotype was also estimated risk factor for osteoporosis in Turkish postmenopausal women (p = 0.026). To our knowledge, this is the first report to examine IL-10 gene −597 C>A polymorphism and osteoporosis in Turkish population. 相似文献
110.