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目的 探讨高血压合并糖耐量减低(IGT)对老年男性人群全因死亡风险的影响。方法 纳入2005年5月至2007年5月在解放军总医院第二医学中心行口服葡萄糖耐量试验检出的老年男性IGT患者和正常糖耐量(NGT)人群,根据基线时是否存在高血压病史和IGT分为4组:非高血压(NH)+正常糖耐量(NGT)组、高血压(H)+NGT组、NH+IGT组、H+IGT组,每年至少随访1次。采用SPSS 13.0统计软件进行数据分析。采用Cox回归模型分析不同组别全因死亡风险的差异。结果 与NH+NGT组比较,H+IGT组(HR=2.55,95%CI 1.56-4.16; P<0.001)和NH+IGT组(HR=2.40,95%CI 1.35-4.25; P=0.003)2型糖尿病发病风险显著升高。单因素Cox比例风险回归分析提示,与NH+NGT组比较,H+IGT组(HR=2.59,95%CI 1.34-5.01; P=0.005)全因死亡风险明显升高,而H+NGT组和NH+IGT组无统计学差异(P>0.05)。在调整相关危险因素后多因素Cox比例风险回归分析显示,H+IGT组(HR=1.83,95%CI 0.90-3.70; P=0.095)全因死亡风险较NH+NGT组虽无统计学差异(P>0.05),但有升高的趋势。结论 老年男性人群高血压合并IGT与全因死亡风险密切相关,高血压与IGT并存可导致全因死亡风险增加。  相似文献   
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BackgroundsFocal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are very frequently associated with epilepsy in pediatric patients. Human leukocyte immunoglobulin-like receptor B2 (LILRB2) participates in the process of neurite growth, synaptic plasticity, and inflammatory reaction, suggesting a potential role of LILRB2 in epilepsy. However, little is known about the distribution and expression of LILRB2 in cortical lesions of FCD IIb and cortical tubers of TSC.MethodsIn this study, we have described the distribution and expression of LILRB2 signaling pathway in cortical lesions of pediatric patients with FCD IIb (n = 15) and TSC (n = 12) relative to age-matched autopsy control samples (CTX, n = 10), respectively. The protein levels of LILRB2 pathway molecules were assessed by western blotting and immunohistochemistry. The expression pattern was investigated by immunohistochemistry and double labeling experiment. Spearman correlation analysis to explore the correlation between LILRB2 protein level and seizure frequency.ResultsThe protein levels of LILRB2 and its downstream molecules POSH, SHROOM3, ROCK1, ROCK2 were increased in cortices of patients compared to CTX. Protein levels of LILRB2 negatively correlated with the frequency of seizures in FCD IIb and TSC patients, respectively. Moreover, all LILRB2 pathway molecules were strongly expressed in dysmorphic neurons, balloon cells, and giant cells, LILRB2 co-localized with neuron marker and astrocyte marker.ConclusionTaken together, the special expression patterns of LILRB2 signaling pathway in cortical lesions of FCD IIb and TSC implies that it may be involved in the process of epilepsy.  相似文献   
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Agricultural biomass residues are emerged from harvesting and processing of agricultural crops. When the crop production increases, a large amount of biomass residues is produced and remained after cutting of peel, bunch, straw and stalk of crops. In this work, agricultural biomass residues (cassava rhizome, durian peel, pineapple peel and corncob) were selected as feedstock for carbon-rich biochar (CRB) production using a facile pyrolysis method. Proximate analysis and thermogravimetric analysis (TGA) were used to characterize biomass feedstock. The results showed that the percentage of fixed carbon in biomass feedstock ranged between 11.91% and 17.51%. Characteristic differences of the CRB were investigated using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. The carbon content in the CRB was found to significantly depend on biomass origin. Interestingly, cassava rhizome, which has a higher percentage of fixed carbon, is a superior precursor for CRB production. The study of different pyrolysis temperature indicated that the carbon content of cassava rhizome derived CRB is increased with pyrolysis temperature. The tensile properties of composite between poly(lactic acid) PLA and different types of biomass-derived CRB were investigated. PLA composite incorporated with a higher carbon content-CRB tended to exhibit improved mechanical properties. Specifically, the elastic modulus and impact energy of PLA/CRB composite specimens increased remarkably with the incorporation of CRB powder. The current research indicates that CRB prepared from agricultural biomass residues could be a sustainable material for utilization in PLA biocomposites.  相似文献   
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Eosinophils are multifaceted immune cells with diverse functions that enhance allergic inflammation. Cysteinyl leukotrienes (cys-LTs), mainly synthesized in eosinophils, are a class of inflammatory lipid mediators produced via multiple enzymatic reactions from arachidonic acid. Multiple clinical studies have reported dysregulated fatty acid metabolism in severe asthma and aspirin-exacerbated respiratory diseases. Therefore, understanding the mechanism responsible for this metabolic abnormality has attracted a lot of attention. In eosinophils, various stimuli (including cytokines, chemokines, and pathogen-derived factors) prime and/or induce leukotriene generation and secretion. Cell–cell interactions with component cells (endothelial cells, epithelial cells, fibroblasts) also enhance this machinery to augment allergic responses. Nasal polyp-derived eosinophils from patients with eosinophilic rhinosinusitis present a characteristic fatty acid metabolism with selectively higher production of leukotriene D4. Interestingly, type 2 cytokines and microbiome components might be responsible for this metabolic change with altered enzyme expression. Here, we review the regulation of fatty acid metabolism, especially cys-LT metabolism, in human eosinophils toward allergic inflammatory status.  相似文献   
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Pontocerebellar hypoplasia (PCH) encompasses a group of neurodegenerative disorders. There are ten known subtypes with common characteristics of pontine and cerebellar hypoplasia or atrophy, neocortical atrophy, and microcephaly. PCH is associated with anterior horn cell degeneration in PCH1a and PCH1b due to mutations in the VRK1 and EXOSC3 genes. Late onset PCH1 has been described in single case reports. The molecular etiology remains mostly unknown. We describe two siblings from a consanguineous Moslem Arabic family with a unique combination of progressive cerebellar atrophy and a SMA-like anterior horn cell degeneration due to a homozygous mutation in the PLA2G6 gene (NM_003560.2). The PLA2G6 gene encodes phospholipase A2 beta, which is involved in the remodeling of membrane phospholipids, signal transduction and calcium signaling, cell proliferation and apoptosis. Mutations in PLA2G6 are known to cause Neurodegeneration with brain iron accumulation 2 (NBIA2): Our patients have some similarities with NBIA2; both are characterized by rapidly progressive psychomotor regression and cerebellar atrophy. However, NBIA2 is not known to exhibit anterior horn cell degeneration.Our patients' phenotype is more consistent with late onset PCH1; thus, indicating that the spectrum of clinical and radiological presentations of PLA2G6 mutations should be extended and that this gene should be included in the molecular evaluation of patients with late onset PCH1.  相似文献   
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Our work aimed at evaluating the use of permeability glycoprotein (P-gp) inhibiting nanoparticles (NPs) as a part of a suitable oral solid dosage to improve bioavailability. Famotidine (Pepcid®), a stomach acid production inhibitor, was used as a drug model to test our hypothesis. Famotidine-loaded NPs were prepared by solvent emulsion evaporation using PEG grafted on a polylactide acid (PLA) polymer backbone (PLA-g-PEG), with a 5% molar ratio of PEG versus lactic acid monomer and PEG of either 750 or 2000?Da molecular weight. Tablet formulation was composed of 40% Famotidine-loaded NPs, 52.5% microcrystalline cellulose as filler, 7% pre-gelatinized starch as binder/disintegrant, and 0.5% magnesium stearate as lubricant. Tablets containing 1.6?mg of Famotidine were prepared at an average weight of 500?mg, thickness of 6.2–6.5?mm, hardness of 5–8?kp, and disintegration time of <1?min. Our results suggest that Famotidine-loaded NPs using grafted PEG-g-PLA polymers can be formulated as an oral solid dosage form while effectively inhibiting P-gp mediated Famotidine efflux, irrespective of PEG molecular weights. This could therefore represent an attractive formulation alternative to enhance oral permeability and bioavailability of drugs that are P-gp substrates.  相似文献   
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Renal cell carcinoma (RCC) treatment has improved in the last decade with the introduction of drugs targeting tumor angiogenesis. However, the 5-year survival of metastatic disease is still only 10–15%. Here, we explored the prognostic significance of compartment-specific expression of Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF). NRP1 expression was analyzed in RCC tumor vessels, in perivascular tumor cells, and generally in the tumor cell compartment. Moreover, complex formation between NRP1 and the main VEGF receptor, VEGFR2, was determined. Two RCC tissue microarrays were used; a discovery cohort consisting of 64 patients and a validation cohort of 314 patients. VEGFR2/NRP1 complex formation in cis (on the same cell) and trans (between cells) configurations was determined by in situ proximity ligation assay (PLA), and NRP1 protein expression in three compartments (endothelial cells, perivascular tumor cells, and general tumor cell expression) was determined by immunofluorescent staining. Expression of NRP1 in perivascular tumor cells was explored as a marker for RCC survival in the two RCC cohorts. Results were further validated using a publicly available gene expression dataset of clear cell RCC (ccRCC). We found that VEGFR2/NRP1 trans complexes were detected in 75% of the patient samples. The presence of trans VEGFR2/NRP1 complexes or perivascular NRP1 expression was associated with a reduced tumor vessel density and size. When exploring NRP1 as a biomarker for RCC prognosis, perivascular NRP1 and general tumor cell NRP1 protein expression correlated with improved survival in the two independent cohorts, and significant results were obtained also at the mRNA level using the publicly available ccRCC gene expression dataset. Only perivascular NRP1 expression remained significant in multivariable analysis. Our work shows that perivascular NRP1 expression is an independent marker of improved survival in RCC patients, and reduces tumor vascularization by forming complexes in trans with VEGFR2 in the tumor endothelium. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.  相似文献   
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