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Incipient angiogenesis in Barrett's epithelium and lymphangiogenesis in Barrett's adenocarcinoma. 总被引:14,自引:0,他引:14
Merja I Auvinen Eero I T Sihvo Terhi Ruohtula Jukka T Salminen Aki Koivistoinen P?ivi Siivola Ragna R?nnholm Juhani O R?m? Mathias Bergman Jarmo A Salo 《Journal of clinical oncology》2002,20(13):2971-2979
PURPOSE: Barrett's esophagus (BE), a precancerous condition for Barrett's adenocarcinoma, is classically characterized by flames of salmon-colored mucosa extending into normal pale esophageal mucosa. This flaming is thought to be a consequence of continuous erosis of mucosa caused by chronic reflux. Another characteristic feature of Barrett's adenocarcinoma patients is the frequent development of lymph node metastases. We addressed whether onset of angiogenesis occurs in BE and if the lymphatic system might provide a route for Barrett's adenocarcinoma cells to infiltrate regular lymph nodes. PATIENTS AND METHODS: Fifteen surgically resected Barrett's dysplasia or adenocarcinoma patients were included. Immunohistochemistry and a modified whole mount analysis were used. RESULTS: The incipient angiogenesis originates from the pre-existing vascular network in the lamina propria and infiltrates Barrett's epithelium, giving its ominous salmon-red color. Barrett's epithelium-specific goblet cells express vascular endothelial growth factor (VEGF)-A. The immature blood vessels show a relative absence of smooth muscle actin (SMA)-positive mural cells and express VEGF receptor (VEGFR)-2 and matrix metalloproteinase (MMP)-9 on their exterior. Coexpression of VEGF-C and its receptor VEGFR-3 on lymphatic vessels is demonstrated. CONCLUSION: BE is strongly neovascularized not eroded. This novel concept of a molecular mechanism of the origin of BE might emphasize why precancerous BE can give rise to the more cancerous dysplasia and Barrett's adenocarcinoma stages. In addition, adenocarcinoma cells induce lymphangiogenesis. The new lymphangiogenic vessels might provide a systemic route for adenocarcinoma cells to invade circulation and induce lymph node metastasis. 相似文献
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Evaluation of the chronic toxicity and oncogenicity of N,N-diethyl-m- toluamide (DEET) 总被引:1,自引:0,他引:1
Schoenig GP; Osimitz TG; Gabriel KL; Hartnagel R; Gill MW; Goldenthal EI 《Toxicological sciences》1999,47(1):99-109
Chronic toxicity and/or oncogenicity studies were conducted in rats, mice,
and dogs with the insect repellent DEET. DEET was mixed in the diet and
administered to CD rats for two years at concentrations that corresponded
to dosage levels of 10, 30 or 100 mg/kg/day for males and 30, 100, or 400
mg/kg/day for females; to CD-1 mice for 18 months at dosage levels of 250,
500, or 1000 mg/kg/day; and to dogs for one year, via gelatin capsules, at
dosage levels of 30, 100, or 400 mg/kg/day. In the rodent studies, each
group consisted of 60 animals of each sex, and two concurrent independent
control groups, each containing 60 animals/sex were included in each study.
Each group in the dog study consisted of four male and four female dogs and
one control group was included in the study. Treatment-related effects were
observed at the highest dose level in all three studies. For rats, the
effects included decreases in body weight and food consumption and an
increase in serum cholesterol in females only. In mice, the effects
observed were decreases in body weight and food consumption in both sexes.
The effects observed in dogs included increased incidences of emesis and
ptyalism, and levels of transient reduction in hemoglobin and hematocrit,
increased alkaline phosphatase (males only), decreased cholesterol, and
increased potassium. One male dog in the high-dose group also exhibited
ataxia, tremors, abnormal head movements, and/or convulsions on several
occasions during the study. The highest no- observed-effect levels (NO-ELs)
for rats, mice and dogs were determined to be 100, 500, and 100 mg/kg/day,
respectively. No specific target organ toxicity or oncogenicity was
observed in any of the studies.
相似文献
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Anna Lautamki Jarmo Gunn Jussi Sipil Pivi Rautava Eero Sihvo Ville Kyt 《Interactive Cardiovascular and Thoracic Surgery》2021,32(6):889
Open in a separate windowOBJECTIVESSurgery is the standard treatment in early-stage non-small-cell lung cancer and select cases of small-cell lung cancer, but gender differences in its use and outcome are poorly known. Gender differences in surgical resection rates and long-term survival after lung cancer surgery were therefore investigated. METHODSIn Finland, 3524 patients underwent resection for primary lung cancer during 2004–2014. Surgical rate and mortality data were retrospectively retrieved from 3 nationwide compulsory registries. Survival was studied by comparing propensity-matched cohorts. Median follow-up was 8.6 years.RESULTSSurgery rate was higher in women (15.9% vs 12.3% in men, P < 0.0001). Overall survival was 85.3% 1 year, 51.4% 5 years, 33.4% 10 years and 24.2% at 14 years from surgery. In matched groups, survival after resection was better in women after 1 year (91.3% vs 83.3%), 5 years (60.2% vs 48.6%), 10 years (43.7% vs 27.9%) and 14 years (29.0% vs 21.1%) after surgery [hazard ratio (HR) 0.66; confidence interval (CI) 0.58–0.75; P < 0.0001]. Of all first-year survivors, 39.1% were alive 10 years and 28.3% 14 years after surgery. Among these matched first-year survivors, women had higher 14-year survival (36.9% vs 25.3%; HR 0.75; CI 0.65–0.87; P = 0.0002).CONCLUSIONSSurgery is performed for lung cancer more often in women. Women have more favourable short- and long-term outcome after lung cancer surgery. Gender discrepancy in survival continues to increase beyond the first year after surgery. 相似文献
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目的观察1,25-二羟维生素D3[1,25-(OH):D,]对糖尿病大鼠炎性水平及肺组织Toll样受体4(TLR4)表达的影响,探讨其肺保护作用及机制。方法将90只SD大鼠随机分为对照组(C组)10只及模型组80只,模型组经尾静脉注射STZ制备糖尿病模型,C组注射等体积柠檬酸缓冲液;将模型组造模成功的75只大鼠随机分为糖尿病组(D组),1,25-(OH):D,大、中、小剂量干预组(H、M、L组)及精蛋白锌胰岛素干预组(Y组)各15只,其中H、M、L组分别予0.3、0.15、0.025μg/(kg·d)的1,25-(OH):D3灌胃,Y组予胰岛素颈后皮下注射,c组和D组予蒸馏水2mL灌胃,均为1次/d、连续16周,16周后所有动物均采用股动脉放血处死,立即取肺脏组织置于10%甲醛及液氮中保存。测定各组血糖及血清CRP水平;采用HE、Masson染色法观察肺组织形态学变化,免疫组织化学法检测TLR4、NF-KBp65的蛋白表达;采用PCR法定量检测TLR4、MyD88、NF-KBp65的mRNA表达。结果①D组血糖及血清CRP水平均显著高于C组(P〈0.01),各干预组均不同程度低于D组,尤以H组为著(P〈0.01)。②D组肺泡壁重度增厚、肺间质明显增生、大量炎症细胞浸润,H、Y、M及L组肺泡壁轻到中度增厚、炎细胞浸润明显;与c组比较,余5组TLR4、NF-KBp65蛋白表达有所升高,其中H、Y组显著低于D组。③D组,TLR4、MyD88和NF-KBp65的mRNA表达显著高于C组(P〈0.01),各干预组表达水均低于D组。肺组织TLR4mRNA表达与MyD88mRNA(r=0.610)、NF-KBp65mRNA表达(r=0.744)均呈正相关,P均〈0.001;MyD88mRNA与NF-KBp65mRNA表达亦呈正相关(r=0.609),P〈0.001。结论1,25-(OH):D,可能通过TLR4介导的炎症途径对STZ诱导的糖尿病大鼠肺脏病变发挥保护作用。 相似文献