全文获取类型
收费全文 | 1757篇 |
免费 | 83篇 |
国内免费 | 35篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 6篇 |
妇产科学 | 13篇 |
基础医学 | 462篇 |
口腔科学 | 78篇 |
临床医学 | 88篇 |
内科学 | 477篇 |
皮肤病学 | 21篇 |
神经病学 | 91篇 |
特种医学 | 12篇 |
外科学 | 77篇 |
综合类 | 127篇 |
预防医学 | 102篇 |
眼科学 | 12篇 |
药学 | 159篇 |
3篇 | |
中国医学 | 20篇 |
肿瘤学 | 121篇 |
出版年
2023年 | 6篇 |
2022年 | 19篇 |
2021年 | 24篇 |
2020年 | 24篇 |
2019年 | 55篇 |
2018年 | 46篇 |
2017年 | 33篇 |
2016年 | 31篇 |
2015年 | 35篇 |
2014年 | 126篇 |
2013年 | 95篇 |
2012年 | 69篇 |
2011年 | 81篇 |
2010年 | 78篇 |
2009年 | 121篇 |
2008年 | 150篇 |
2007年 | 157篇 |
2006年 | 81篇 |
2005年 | 122篇 |
2004年 | 56篇 |
2003年 | 60篇 |
2002年 | 47篇 |
2001年 | 35篇 |
2000年 | 31篇 |
1999年 | 50篇 |
1998年 | 42篇 |
1997年 | 34篇 |
1996年 | 20篇 |
1995年 | 22篇 |
1994年 | 20篇 |
1993年 | 19篇 |
1992年 | 13篇 |
1991年 | 9篇 |
1990年 | 6篇 |
1988年 | 1篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 8篇 |
1979年 | 4篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1974年 | 3篇 |
1973年 | 1篇 |
排序方式: 共有1875条查询结果,搜索用时 15 毫秒
41.
Bone mineral density improvement after lung volume reduction surgery for severe emphysema 总被引:6,自引:0,他引:6
BACKGROUND: In patients with severe emphysema, bone mineral density (BMD) is reduced and the risk of osteoporosis is increased. STUDY OBJECTIVES: To identify the impact of lung volume reduction surgery on BMD. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS AND INTERVENTIONS: Forty emphysematous patients, all receiving oral steroid therapy, underwent bilateral lung volume reduction surgery. Thirty similar patients, who refused the operation, followed a standard respiratory rehabilitation program. MEASUREMENTS: All subjects were evaluated pretreatment and 12 months posttreatment for respiratory function, nutritional status, and bone-related biochemical parameters. BMD was assessed by dual-energy radiograph absorptiometry. RESULTS: After surgery, we observed significant improvements in respiratory function (FEV1, + 18.8% [p < 0.01]; residual volume [RV], -29.6% [p < 0.001]; diffusing capacity of the lung for carbon monoxide [Dlco], + 21.6% [p < 0.01]) nutritional parameters (fat-free mass, + 6.0% [p < 0.01]), levels of bone-related hormones (free-testosterone, + 20.5% [p < 0.01]; parathormone, -11.2% [p < 0.01]), bone turnover markers (osteocalcin, -12.7% [p < 0.05]; bone-alkaline-phosphatase, -14.0% [p < 0.05]; beta-crosslaps, -33.6% [p < 0.001]), BMD (lumbar, + 8.8% [p < 0.01]; femoral, + 5.5% [p < 0.01]), and T-score (lumbar, + 21.0% [p < 0.01]; femoral, + 12.4% [p < 0.01]) with reduction in osteoporosis rate (50 to 25%). Nineteen patients who had undergone surgery were able to discontinue treatment with oral steroids. These subjects showed a more significant improvement in BMD (lumbar, + 9.6%; femoral, + 6.8%; p < 0.001) and T-score (lumbar, + 27.3%; femoral, + 14.3%; p < 0.001). The remaining 21 patients who had undergone surgery experienced significant improvement compared to respiratory rehabilitation subjects despite continued therapy with oral steroids (BMD: lumbar, + 4.5% vs -0.7%, respectively [p < 0.01]; femoral, + 2.7% vs -1.1%, respectively [p < 0.05]; T-score: lumbar, + 14 vs -2.1, respectively [p < 0.01]; femoral, + 7.4 vs -2.7, respectively [p < 0.01]). The increase in lumbar BMD was correlated with the surgical reduction of RV (p = 0.02) and with the increase in Dlco (p = 0.01) and fat-free mass (p = 0.01). CONCLUSIONS: Lung volume reduction surgery significantly improves BMD compared to respiratory rehabilitation therapy, even in patients requiring oral steroids. The increase in BMD correlates with RV, Dlco, and fat-free mass, suggesting that the restoration of respiratory dynamics, gas exchange, and nutritional status induces improvement in bone metabolism and mineral content. 相似文献
42.
Reinehr R Becker S Keitel V Eberle A Grether-Beck S Häussinger D 《Gastroenterology》2005,129(6):2009-2031
BACKGROUND & AIMS: Hydrophobic bile salts trigger a rapid oxidative stress response as an upstream event of CD95 activation and hepatocyte apoptosis. METHODS: The underlying mechanisms were studied by Western blot, immunocytochemistry, protein knockdown, and fluorescence resonance energy transfer microscopy in rat hepatocytes and human hepatoma cell line 7 (Huh7). RESULTS: The rapid oxidative stress formation in response to taurolithocholate-3-sulfate (TLCS) was inhibited by diphenyleneiodonium, apocynin, and neopterin, suggestive for the involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. TLCS induced a rapid serine phosphorylation of the regulatory subunit p47phox, which was sensitive to inhibition of sphingomyelinase and protein kinase Czeta (PKCzeta). Inhibitors of p47phox phosphorylation and p47phox protein knockdown abolished the TLCS-induced oxidative stress response and blunted subsequent CD95 activation. Consequences of TLCS-induced oxidative stress were c-Jun-N-terminal kinase activation and Yes-dependent activation of the epidermal growth factor receptor (EGFR), followed by EGFR-catalyzed CD95 tyrosine phosphorylation, formation of the death-inducing signaling complex, and execution of apoptosis. As shown by fluorescence resonance energy transfer experiments in Huh7 cells, TLCS induced a c-Jun-N-terminal kinase-dependent EGFR/CD95 association in the cytosol and trafficking of this protein complex to the plasma membrane. Inhibition of EGFR tyrosine kinase activity by AG1478 allowed for cytosolic EGFR/CD95 association, but prevented targeting of the EGFR/CD95 complex to the plasma membrane. Both processes, and TLCS-induced Yes and EGFR activation, were sensitive to inhibition of sphingomyelinase, PKCzeta, or NADPH oxidases. CONCLUSIONS: The data suggest that hydrophobic bile salts activate NADPH oxidase isoforms with the resulting oxidative stress response triggering activation of the CD95 system and apoptosis. 相似文献
43.
44.
Matthew P. Wood Amy L. Cole Colleen R. Eade Li‐Mei Chen Karl X. Chai Alexander M. Cole 《Immunology》2014,142(3):474-483
Several aspects of HIV‐1 virulence and pathogenesis are mediated by the envelope protein gp41. Additionally, peptides derived from the gp41 ectodomain have been shown to induce chemotaxis in monocytes and neutrophils. Whereas this chemotactic activity has been reported, it is not known how these peptides could be produced under biological conditions. The heptad repeat 1 (HR1) region of gp41 is exposed to the extracellular environment and could therefore be susceptible to proteolytic processing into smaller peptides. Matriptase is a serine protease expressed at the surface of most epithelia, including the prostate and mucosal surfaces. Here, we present evidence that matriptase efficiently cleaves the HR1 portion of gp41 into a 22‐residue chemotactic peptide MAT‐1, the sequence of which is highly conserved across HIV‐1 clades. We found that MAT‐1 induced migration of primary neutrophils and monocytes, the latter of which act as a cellular reservoir of HIV during early stage infection. We then used formyl peptide receptor 1 (FPR1) and FPR2 inhibitors, along with HEK 293 cells, to demonstrate that MAT‐1 can induce chemotaxis specifically using FPR2, a receptor found on the surface of monocytes, macrophages and neutrophils. These findings are the first to identify a proteolytic cleavage product of gp41 with chemotactic activity and highlight a potential role for matriptase in HIV‐1 transmission and infection at epithelial surfaces and within tissue reservoirs of HIV‐1. 相似文献
45.
Lili Zhang Marianne Gallup Lorna Zlock Yu Ting Feeling Chen Walter E Finkbeiner Nancy A McNamara 《The Journal of pathology》2014,234(1):60-73
Cigarette smoke increases the risk of lung cancer by 20‐fold and accounts for 87% of lung cancer deaths. In the normal airway, heavily O‐glycosylated mucin‐1 (MUC1) and adherens junctions (AJs) establish a structural barrier that protects the airway from infectious, inflammatory and noxious stimuli. Smoke disrupts cell–cell adhesion via its damaging effects on the AJ protein epithelial cadherin (E‐cad). Loss of E‐cad is a major hallmark of epithelial–mesenchymal transition (EMT) and has been reported in lung cancer, where it is associated with invasion, metastasis and poor prognosis. Using organotypic cultures of primary human bronchial epithelial (HBE) cells treated with smoke‐concentrated medium (Smk), we have demonstrated that E‐cad loss is regulated through the aberrant interaction of its AJ binding partner, p120‐catenin (p120ctn), and the C‐terminus of MUC1 (MUC1‐C). Here, we reported that even before MUC1‐C became bound to p120ctn, smoke promoted the generation of a novel 400 kDa glycoform of MUC1's N‐terminus (MUC1‐N) differing from the 230 kDa and 150 kDa glycoforms in untreated control cells. The subsequent smoke‐induced, time‐dependent shedding of glycosylated MUC1‐N exposed MUC1‐C as a putative receptor for interactions with EGFR, Src and p120ctn. Smoke‐induced MUC1‐C glycosylation modulated MUC1‐C tyrosine phosphorylation (TyrP) that was essential for MUC1‐C/p120ctn interaction through dose‐dependent bridging of Src/MUC1‐C/galectin‐3/EGFR signalosomes. Chemical deglycosylation of MUC1 using a mixture of N‐glycosylation inhibitor tunicamycin and O‐glycosylation inhibitor benzyl‐α‐GalNAc disrupted the Src/MUC1‐C/galectin‐3/EGFR complexes and thereby abolished smoke‐induced MUC1‐C‐TyrP and MUC1‐C/p120ctn interaction. Similarly, inhibition of smoke‐induced MUC1‐N glycosylation using adenoviral shRNA directed against N‐acetyl‐galactosaminyl transferase‐6 (GALNT6, an enzyme that controls the initiating step of O‐glycosylation) successfully suppressed MUC1‐C/p120ctn interaction, prevented E‐cad degradation and maintained cellular polarity in response to smoke. Thus, GALNT6 shRNA represents a potential therapeutic modality to prevent the initiation of events associated with EMT in the smoker's airway. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
46.
为预测EB病毒(EBV)gp350/220抗原T-B联合表位,采用在线软件IEDB和SYFPEITHIT分别预测gp350/220抗原B细胞表位和T细胞表位,寻找该抗原B细胞和T细胞共同的区域即T-B联合表位。gp350/220抗原存在潜在的T-B联合表位区域:28-43、49-55、59-64、69-79、85-91、99-111、119-129、135-144。本文运用生物信息学方法确定了gp350/220分别存在5个T细胞抗原表位﹑6个B细胞表位和3个T-B细胞联合表位区域,为进一步研发gp350/220高价优势表位疫苗奠定基础。 相似文献
47.
48.
49.
50.