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61.
Elisavet Lioulia Panagiotis Mokos Emmanuel Panteris Dimitra Dafou 《Molecular oncology》2022,16(8):1694
Ubiquitin‐conjugating enzyme E2T (UBE2T) has been implicated in many types of cancer including hepatocellular carcinoma (HCC). Epithelial–mesenchymal transition (EMT) process plays a fundamental role during tumor metastasis and progression. However, the molecular mechanisms underlying EMT in HCC in accordance with UBE2T still remain unknown. In this study, we showed that UBE2T overexpression augmented the oncogenic properties and specifically EMT in HCC cell lines, while its silencing attenuated them. UBE2T affected the activation of EMT‐associated signaling pathways: MAPK/ERK, AKT/mTOR, and Wnt/β‐catenin. In addition, we revealed that the epithelial protein complex of E‐cadherin/β‐catenin, a vital regulator of signal transduction in tumor initiation and progression, was totally disrupted at the cell membrane. In particular, we observed that UBE2T overexpression led to E‐cadherin loss accompanied by a simultaneous elevation of both cytoplasmic and nuclear β‐catenin, while its silencing resulted in a strong E‐cadherin turnover at the cell membrane. Interestingly, chemical inhibition of the MAPK/ERK, AKT/mTOR, and Wnt/β‐catenin signaling pathways demonstrated that the nuclear translocation of β‐catenin and subsequent EMT was enhanced mainly by MAPK/ERK. Collectively, our findings demonstrate the UBE2T/MAPK‐ERK/β‐catenin axis as a critical regulator of cell state transition and EMT in HCC. 相似文献
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Marinović B Mokos ZB Basta-Juzbasić A Jukić IL Loncarić D Hashimoto T Pasić A 《Acta dermatovenerologica Croatica : ADC》2005,13(4):233-236
Pemphigus vulgaris is an organ-specific autoimmune mucocutaneous disorder. In the majority of cases, the disease manifests initially with oral lesions, and may be limited to a single site for months before spreading. A 78-year-old woman with yellowish crusted areas on her left preauricular region and close to the medial angle of her right eye is presented. Although she described an episode of erosions on her lower lip, the involvement of mucosal surfaces was not noticed on examination. Before she presented to our Department, she was misdiagnosed as an actinic cheilitis and malignant skin tumor. Histopathologic examination and direct immunofluorescence confirmed the diagnosis of pemphigus vulgaris. Immunoblotting of epidermal extracts detected IgG antibodies against desmoglein 3 but not desmoglein 1, which was also confirmed by ELISA test. The patient responded favorably to systemic corticosteroid therapy combined with adjuvant immunosuppressive therapy, with complete clearance of the lesions. 相似文献
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目的:观察柯萨奇B3病毒性心肌炎小鼠心肌组织的病理特点及胶原蛋白的表达情况。方法:实验于2004-10/2006-04在广西医科大学医学科学实验中心完成。①实验分组:选择80只Balb/c纯种雄性小鼠,鼠龄4 ̄6周,随机分为对照组20只和模型组60只。②实验方法:模型组小鼠腹腔注射柯萨奇B3Nancy株悬液0.1mL,对照组腹腔注射不含病毒的Hep-2细胞冻存液0.1mL。模型组小鼠分别于接种柯萨奇B3后第7,14,28和42天麻醉后断颈处死10只,10只,10只和9只,颈动脉采血0.8 ̄1.0mL,保存血清;摘取心脏,浸泡于4%多聚甲醛溶液中;对照组20只小鼠于42d后采用上述方法处死,并留取血清及心脏。③实验评估:检测血清CVB3中和抗体滴度;心肌组织切片苏木精-伊红染色后,光镜下观察组织形态学改变;免疫组化法检测心肌Ⅰ型和Ⅲ型胶原蛋白的表达情况。结果:①行为学变化及死亡情况:模型组于接种后第3天出现行为学改变,第12天后症状逐渐缓解;从第4天开始发生死亡,第7 ̄10天为死亡高峰期,第12天后无死亡,总死亡率为35%(21/60)。②血清柯萨奇B3中和抗体滴度:模型组各时间点血清柯萨奇B3中和抗体滴度均高于对照组(P<0.01),以第7天滴度为最高。③心肌组织形态学特点:接种病毒后7d,心肌组织出现多灶性凝固性坏死,大量炎细胞浸润;28d后,坏死灶周围的炎细胞已近消失,代之以增殖的成纤维细胞。④心肌组织病理积分:模型组各时间点心肌病理积分均明显高于对照组,其中第7天增高最为显著(P<0.05)。⑤心肌组织Ⅰ型和Ⅲ型胶原蛋白表达:模型组各时间点心肌组织Ⅰ型和Ⅲ型胶原蛋白表达均明显增加,以第42天最为显著(P<0.01);第7天和第14天小鼠心肌Ⅰ/Ⅲ型胶原比值与对照组之间无显著性差别(P>0.05),而第28天和第42天则显著高于对照组(P<0.05)。结论:采用腹腔注射柯萨奇B3Nancy株悬液的方法可以成功构建病毒性心肌炎小鼠模型。病理表现为急性期心肌细胞大量坏死,伴多种炎细胞浸润,胶原蛋白表达活跃;缓解期,成纤维细胞大量增殖,胶原蛋白表达持续增高,最终导致心肌间质重构。 相似文献
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雷公藤甲素含药血清对大鼠成纤维样滑膜细胞增殖及其巨噬细胞移动抑制因子表达的影响 总被引:1,自引:0,他引:1
目的:雷公藤甲素是雷公藤抗炎、抗肿瘤、免疫调节和抑制细胞增殖的主要有效成分。观察雷公藤甲素、雷公藤及其与来氟米特配伍的含药血清对大鼠成纤维样滑膜细胞的增殖及巨噬细胞移动抑制因子表达的影响。方法:实验于2006-12/2007-03在解放军白求恩国际和平医院中心实验室完成。①实验分组:雄性Wistar大鼠12只,体质量150~180g,随机数字表法分为6组,分别为雷公藤组、雷公藤甲素组、来氟米特组、雷公藤 来氟米特组、雷公藤甲素 来氟米特组和空白对照组,每组2只。②实验方法:雷公藤组、雷公藤甲素组、来氟米特组、雷公藤 来氟米特组、雷公藤甲素 来氟米特组,分别将雷公藤、雷公藤甲素、雷公藤 来氟米特、雷公藤甲素 来氟米特的含药血清以0.1、0.2、0.3的体积分数干预成纤维样滑膜细胞,空白对照组加入正常鼠血清。③实验评估:四甲基偶氮唑盐比色法观察细胞增殖情况;免疫组织化学染色及细胞ELISA法检测滑膜细胞和细胞上清液巨噬细胞移动抑制因子的表达。结果:纳入大鼠12只,均进入结果分析。①四甲基偶氮唑盐比色法结果显示,含药血清对体外滑膜细胞增殖具有显著抑制作用,单药最佳作用体积分数为0.2。②雷公藤甲素组、雷公藤组、雷公藤甲素 来氟米特组、雷公藤 来氟米特组的含药血清对成纤维样滑膜细胞均具有显著抗增殖效应,以体积分数为0.1雷公藤甲素联合体积分数为0.3来氟米特的含药血清抑制作用最强,与空白对照组相比,差异具有显著性意义(P<0.05)。③对巨噬细胞移动抑制因子蛋白表达的抑制作用则以雷公藤甲素 来氟米特的含药血清最佳,与其他各组相比,差异均有显著性(P<0.05)。结论:雷公藤甲素是雷公藤抑制成纤维样滑膜细胞增殖和抗炎作用的主要有效成分,而雷公藤甲素 来氟米特组的含药血清在抑制成纤维样滑膜细胞增殖及其表达巨噬细胞移动抑制因子等方面显示出明显的协同/增效作用。 相似文献
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炎症性肠病基因治疗进展 总被引:1,自引:0,他引:1
0 引言 溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD)都属于炎症性肠病(inflammatory bowel disease,IBD),其发病可能由感染、遗传、免疫等多种因素相互作用所致.传统观念认为通过基因转移替代缺陷基因的基因治疗只适用于致病基因明确的疾病,目前慢性炎症性疾病和自身免疫性疾病也被纳入了基因治疗的范围,可通过基因转移使机体表达免疫相关蛋白质,从而下调致病的炎症和免疫反应,上调保护性反应.相对于囊性纤维化、重症联合免疫缺陷和肿瘤,IBD的基因治疗尚处于起步阶段.本文就IBD的基因治疗作一概述. 相似文献
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Bukvić Mokos Z Lipozenčić J Ceović R Stulhofer Buzina D Kostović K 《Acta dermatovenerologica Croatica : ADC》2010,18(3):185-189
Although frequently performed, laser removal of pigmented lesions still contains certain controversial issues. Epidermal pigmented lesions include solar lentigines, ephelides, café au lait macules and seborrheic keratoses. Dermal lesions include melanocytic nevi, blue nevi, drug induced hyperpigmentation and nevus of Ota and Ito. Some lesions exhibit both an epidermal and dermal component like Becker's nevus, postinflammatory hyperpigmentations, melasma and nevus spilus. Due to the wide absorption spectrum of melanin (500-1100 nm), several laser systems are effective in removal of pigmented lesions. These lasers include the pigmented lesion pulsed dye laser (510 nm), the Q-switched ruby laser (694 nm), the Q-switched alexandrite laser (755 nm) and the Q-switched Nd:YAG laser (1064 nm), which can be frequency-doubled to produce visible green light with a wavelength of 532 nm. The results of laser therapy are usually successful. However, there are still many controversies regarding the use of lasers in treating certain pigmented lesions. Actually, the essential question in removing pigmented lesions with lasers is whether the lesion has atypical features or has a malignant potential. Dermoscopy, used as a routine first-level diagnostic technique, is helpful in most cases. If there is any doubt whether the lesion is benign, then a biopsy for histologic evaluation is obligatory. 相似文献
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