全文获取类型
收费全文 | 541篇 |
免费 | 68篇 |
国内免费 | 43篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 9篇 |
妇产科学 | 5篇 |
基础医学 | 79篇 |
口腔科学 | 14篇 |
临床医学 | 40篇 |
内科学 | 54篇 |
皮肤病学 | 10篇 |
神经病学 | 118篇 |
特种医学 | 10篇 |
外科学 | 25篇 |
综合类 | 128篇 |
预防医学 | 12篇 |
眼科学 | 24篇 |
药学 | 46篇 |
中国医学 | 50篇 |
肿瘤学 | 23篇 |
出版年
2024年 | 3篇 |
2023年 | 7篇 |
2022年 | 10篇 |
2021年 | 20篇 |
2020年 | 23篇 |
2019年 | 20篇 |
2018年 | 22篇 |
2017年 | 28篇 |
2016年 | 17篇 |
2015年 | 34篇 |
2014年 | 42篇 |
2013年 | 51篇 |
2012年 | 61篇 |
2011年 | 58篇 |
2010年 | 37篇 |
2009年 | 39篇 |
2008年 | 47篇 |
2007年 | 37篇 |
2006年 | 25篇 |
2005年 | 15篇 |
2004年 | 13篇 |
2003年 | 18篇 |
2002年 | 11篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 1篇 |
1997年 | 3篇 |
排序方式: 共有652条查询结果,搜索用时 15 毫秒
101.
Yoko Shida Hisafumi Matsuoka Motoko Chiga Shinichi Uchida Sei Sasaki Shigetaka Sugihara 《Pediatrics international》2013,55(1):105-107
We identified the AQP‐2 gene mutation (R254Q) in a family with dominant NDI. The patient studied here has NDI with partial response to the anti‐diuretic effect of AVP and dDAVP. Hereditary NDI seems to have the uniform clinical manifestations, but this might only reflect the information on screened patients with clear clinical presentations. It may be that a milder form of NDI has been overlooked due to a lack of genetic identification. Gene mutation analysis should be considered even in patients with mild NDI symptoms. Fortunately, both V2R and AQP2 genes are small and can be easily analyzed. 相似文献
102.
103.
结直肠癌(colorectal cancer,CRC)的发病率和死亡率逐年上升,水通道蛋白是一类存在于细胞膜上的膜转运蛋白,参与缺氧肿瘤微环境中肿瘤细胞的增殖、侵袭和转移等过程,甚至与肿瘤耐药性相关。结直肠癌患者中存在多种水通道蛋白的表达失调,在肿瘤的发生和发展过程中发挥关键作用。随着精准治疗的开展,将水通道蛋白作为新靶点可能为结直肠癌的治疗提供新途径。本文就水通道蛋白(aquaporins,AQPs)在结直肠癌缺氧微环境中的表达及其临床意义作一综述。 相似文献
104.
Cao C Yu X Liao Z Zhu N Huo H Wang M Ji G She H Luo Z Yue S 《Critical care (London, England)》2012,16(5):R186
Introduction
Three percent sodium chloride (NaCl) treatment has been shown to reduce brain edema and inhibited brain aquaporin 4 (AQP4) expression in bacterial meningitis induced by Escherichia coli. Lipopolysaccharide (LPS) is the main pathogenic component of E. coli. We aimed to explore the effect of 3% NaCl in mouse brain edema induced by LPS, as well as to elucidate the potential mechanisms of action.Methods
Three percent NaCl was used to treat cerebral edema induced by LPS in mice in vivo. Brain water content, IL-1β, TNFα, immunoglobulin G (IgG), AQP4 mRNA and protein were measured in brain tissues. IL-1β, 3% NaCl and calphostin C (a specific inhibitor of protein kinase C) were used to treat the primary astrocytes in vitro. AQP4 mRNA and protein were measured in astrocytes. Differences in various groups were determined by one-way analysis of variance.Results
Three percent NaCl attenuated the increase of brain water content, IL-1β, TNFα, IgG, AQP4 mRNA and protein in brain tissues induced by LPS. Three percent NaCl inhibited the increase of AQP4 mRNA and protein in astrocytes induced by IL-1β in vitro. Calphostin C blocked the decrease of AQP4 mRNA and protein in astrocytes induced by 3% NaCl in vitro.Conclusions
Osmotherapy with 3% NaCl ameliorated LPS-induced cerebral edema in vivo. In addition to its osmotic force, 3% NaCl exerted anti-edema effects possibly through down-regulating the expression of proinflammatory cytokines (IL-1β and TNFα) and inhibiting the expression of AQP4 induced by proinflammatory cytokines. Three percent NaCl attenuated the expression of AQP4 through activation of protein kinase C in astrocytes. 相似文献105.
Wen-Zhen Shi Chun-Zhen Zhao Bing Zhao Qiao-Juan Shi Li-Hui Zhang Yan-Fang Wang San-Hua Fang Yun-Bi Lu Wei-Ping Zhang Er-Qing Wei 《神经科学通报》2012,28(6):680-692
Objective Aquaporin-4(AQP4),the main water channel protein in the brain,plays a critical role in water homeostasis and brain edema.Here,we investigated its role in the inflammatory responses after focal cerebral ischemia. Methods In AQP4-knockout(KO) and wild-type mice,focal cerebral ischemia was induced by 30 min of middle cerebral arterial occlusion(MCAO).Ischemic neuronal injury and cellular inflammatory responses,as well as the expression and localization of cysteinyl leukotriene CysLT2 and CysLT1 receptors,were determined at 24 and 72 h after MCAO. Results AQP4-KO mice showed more neuronal loss,more severe microglial activation and neutrophil infiltration,but less astrocyte proliferation in the brain after MCAO than wild-type mice.In addition,the protein levels of both CysLT1, and CysLT2 receptors were up-regulated in the ischemic brain,and the up-regulation was more pronounced in AQP4-KO mice.The CysLT1,and CysLT2 receptors were primarily localized in neurons,microglia and neutrophils;those localized in microglia and neutrophils were enhanced in AQP4-KO mice.Conclusion AQP4 may play an inhibitory role in postischemic inflammation. 相似文献
106.
Jian Huo Jiachuan Liu Jinbiao Wang Yongming Zhang Chunlin Wang Yanyan Yang Wenjiang Sun Shaonian Xu 《中国神经再生研究》2012,7(22):1729-1735
In the present study, rabbits were treated with hyperbaric oxygen for 1 hour after detonator-blast-induced craniocerebral injury. Immunohistochemistry showed significantly reduced aquaporin 4 expression and adrenocorticotropic hormone expression in the pituitary gland of rabbits with craniocerebral injury. Aquaporin 4 expression was positively correlated with adrenocorticotropic hormone expression. These findings indicate that early hyperbaric oxygen therapy may suppress adrenocorticotropic hormone secretion by inhibiting aquaporin 4 expression. 相似文献
107.
目的:观察鼻腔局部应用丙酸氟替卡松和左卡巴斯汀对实验性变应性鼻炎(AR)大鼠水通道蛋白5(AQP5)表达的影响。方法:40只Wister大鼠随机分为AR组30只和对照组10只。AR组建模后,随机均分为3组:AR+丙酸氟替卡松组(F组)、AR+左卡巴斯汀组(L组)和AR组(10只)。3组大鼠治疗28 d后,应用免疫组织化学检测AQP5在各组中的表达。结果:免疫组织化学显示AQP5在各组分布相同,统计学分析显示F组与AR组、L组比较,差异有统计学意义(P〈0.05),但L组与AR组比较,差异无统计学意义(P〉0.05);L组与对照组比较,差异有统计学意义(P〈0.05)。结论:AQP5在实验性AR大鼠鼻黏膜的强表达,提示AQP5参与了AR的发病过程,与腺体过度分泌、组织水肿有关。糖皮质激素可以明显下调AQP5的表达量,H1受体阻滞剂对AQP5的表达量无明显影响。 相似文献
108.
J. Schnermann 《Acta physiologica (Oxford, England)》2001,173(1):59-66
Animals with induced or natural null mutations in renal NaCl and water transporter genes provide a powerful tool to study the physiological mechanisms that enable the kidney to optimize the match between glomerular filtration rate and tubular reabsorption. Deficiencies in the Na/H exchanger NHE3 and in the water channel aquaporin 1 (AQP1) cause reductions in proximal fluid absorption which are accompanied by proportionate decrements in glomerular filtration rate (GFR). Compensation of the transport defect by a reduction in filtered load is so efficient that clinically symptomatic Na losses are not observed in either NHE3 or AQP1 deficient animals. On the other hand, severe syndromes of salt wasting are caused by loss of function of the Na,K,2Cl‐cotransporter (NKCC2) in the thick ascending limb, or of the epithelial Na channel (ENaC) the collecting duct indicating that the severity of Na dysregulation is unrelated to the basal absorption of NaCl in a given nephron segment. In these states, the increased delivery of Na to downstream segments is not monitored by a sensor linked to the site of filtrate formation. In the absence of adaptations in the filtered load intrarenal compensation of a circumscribed NaCl malabsorption by adjustment of NaCl transport in other nephron segments is sometimes insufficient, particularly in the immature kidney of the newborn. 相似文献
109.
Sbastien Holvoet Sophie Nutten Lnaïck Dupuis Dominique Donnicola Tristan Bourdeau Betsy Hughes-Formella Dagmar Simon Hans-Uwe Simon Ryan S. Carvalho Jonathan M. Spergel Sibylle Koletzko Carine Blanchard 《Nutrients》2021,13(9)
Specific partially hydrolysed whey-based infant formulas (pHF-W) have been shown to decrease the risk of atopic dermatitis (AD) in infants. Historically, AD has been associated primarily with milk allergy; however, defective skin barrier function can be a primary cause of AD. We aimed to ascertain whether oral supplementation with pHF-W can improve skin barrier function. The effect of pHF-W was assessed on transepidermal water loss (TEWL) and antibody productions in mice epicutaneously exposed to Aspergillus fumigatus. Human primary keratinocytes were stimulated in vitro, and the expression of genes related to skin barrier function was measured. Supplementation with pHF-W in neonatal mice led to a significant decrease in TEWL and total IgE, but not in allergen-specific antibody levels. The whey hydrolysate was sufficient to decrease both TEWL and total IgE. Aquaporin-3 gene expression, linked with skin hydration, was modulated in the skin of mice and human primary keratinocytes following protein hydrolysate exposure. Skin barrier improvement may be an additional mechanism by which pHF-W may potentially reduce the risk of AD development in infants. Further human studies are warranted to confirm the clinical efficacy of these observations. 相似文献
110.
Mineo Takagi Keiko Tanaka Tone Suzuki Atsushi Miki Masatoyo Nishizawa Haruki Abe 《Acta ophthalmologica. Supplement》2009,87(5):562-566
Purpose: It has recently been reported that the anti‐aquaporin‐4 antibody (AQP4‐Ab) can be a specific marker of neuromyelitis optica. We present three cases of optic neuritis (ON) where the patients tested positive for AQP4‐Ab, but showed no neurological signs. Methods: Sera were obtained from 32 Japanese patients with ON and no other neurological abnormalities (mean age 46 ± 20 years). AQP4‐Ab was detected by indirect immunofluorescence staining using human‐AQP4‐transfected HEK 293 cells. Results: AQP4‐Ab was positive in three female patients (aged 9, 64 and 82 years). Their illness was characterized by bilateral severe optic nerve involvement, insufficient visual recovery, and autoimmune abnormalities (such as positive antinuclear antibody). Two of these patients experienced recurrent episodes of ON. In at least two episodes, the intracranial portion of the optic nerve showed significant inflammation on magnetic resonance imaging. Conclusions: These cases indicate that some ON patients have an immunological pathogenesis similar to that seen in neuromyelitis optica. In addition, examination for AQP4‐Ab positivity in the initial phase of ON is important in predicting the prognosis, including the possibility of the development of transverse myelitis. 相似文献