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991.
A method to assess the clinical significance of unclassified variants in the BRCA1 and BRCA2 genes based on cancer family history 下载免费PDF全文
Encarna B Gómez García Jan C Oosterwijk Maarten Timmermans Christi J van Asperen Frans BL Hogervorst Nicoline Hoogerbrugge Rogier Oldenburg Senno Verhoef Charlotte J Dommering Margreet GEM Ausems Theo AM van Os Annemarie H van der Hout Marjolijn Ligtenberg Ans van den Ouweland Rob B van der Luijt Juul T Wijnen Jan JP Gille Patrick J Lindsey Peter Devilee Marinus J Blok Maaike PG Vreeswijk 《Breast cancer research : BCR》2009,11(1):R8
Introduction
Unclassified variants (UVs) in the BRCA1/BRCA2 genes are a frequent problem in counseling breast cancer and/or ovarian cancer families. Information about cancer family history is usually available, but has rarely been used to evaluate UVs. The aim of the present study was to identify which is the best combination of clinical parameters that can predict whether a UV is deleterious, to be used for the classification of UVs.Methods
We developed logistic regression models with the best combination of clinical features that distinguished a positive control of BRCA pathogenic variants (115 families) from a negative control population of BRCA variants initially classified as UVs and later considered neutral (38 families).Results
The models included a combination of BRCAPRO scores, Myriad scores, number of ovarian cancers in the family, the age at diagnosis, and the number of persons with ovarian tumors and/or breast tumors. The areas under the receiver operating characteristic curves were respectively 0.935 and 0.836 for the BRCA1 and BRCA2 models. For each model, the minimum receiver operating characteristic distance (respectively 90% and 78% specificity for BRCA1 and BRCA2) was chosen as the cutoff value to predict which UVs are deleterious from a study population of 12 UVs, present in 59 Dutch families. The p.S1655F, p.R1699W, and p.R1699Q variants in BRCA1 and the p.Y2660D, p.R2784Q, and p.R3052W variants in BRCA2 are classified as deleterious according to our models. The predictions of the p.L246V variant in BRCA1 and of the p.Y42C, p.E462G, p.R2888C, and p.R3052Q variants in BRCA2 are in agreement with published information of them being neutral. The p.R2784W variant in BRCA2 remains uncertain.Conclusions
The present study shows that these developed models are useful to classify UVs in clinical genetic practice. 相似文献992.
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广西藤茶中黄酮类成份的提取工艺研究 总被引:18,自引:0,他引:18
目的:提取分离藤(Ampelosis grossdentata)中的双氢杨梅树皮素(dihydromyricetin)和杨梅素(Myricetin)。方法:采用新的水提取和溶剂分离的方法,经化学和光谱鉴定确定结构。结果:提取产物经确证为双氢杨梅树皮素(dihydromyricetin)和杨梅素(Myricetin),平均收率分别为19.6%和0.51%。结论:该提取法经济、简便,易于操作并且提取率 相似文献
995.
David A. Brott Patricia Bentley Murali V.P. Nadella Dale Thurman Jim Fikes Letitia Cheatham Frank McGrath Wenli Luo Lewis B. Kinter 《Toxicology》2013
Alpha 2u-globulin mediated hyaline droplet nephropathy (HDN) is a male rat specific lesion induced when a compound or metabolite binds to alpha 2u-globulin. The objective of this study was to investigate if the newer and more sensitive renal biomarkers would be altered with HDN as well as be able to distinguish between HDN and oxidative stress-induced kidney injury. Rats were dosed orally for 7 days to determine (1) if HDN (induced by 2-propanol or d-limonene) altered the newer renal biomarkers and not BUN or creatinine, (2) if renal biomarkers could distinguish between HDN and oxidative stress-induced kidney injury (induced by potassium bromate), (3) sensitivity of HDN-induced renal biomarker changes relative to d-limonene dose, and (4) reversibility of HDN and renal biomarkers, using vehicle or 300 mg/kg/day d-limonene with 7 days of dosing and necropsies scheduled over the period of Days 8–85. HDN-induced renal biomarker changes in male rats were potentially compound specific: (1) 2-propanol induced mild HDN without increased renal biomarkers, (2) potassium bromate induced moderate HDN with increased clusterin, and (3) d-limonene induced marked HDN with increased αGST, μGST and albumin. Administration of potassium bromate did not result in oxidative stress-induced kidney injury, based on histopathology and renal biomarkers creatinine and BUN. The compound d-limonene induced a dose dependent increase in HDN severity and renal biomarker changes without altering BUN, creatinine or NAG: (1) minimal induction of HDN and no altered biomarkers at 10 mg/kg/day, (2) mild induction of HDN with increased αGST and μGST at 50 mg/kg/day and (3) marked induction of HDN with increased αGST, μGST and albumin at 300 mg/kg/day. HDN induced by d-limonene was reversible, but with a variable renal biomarker pattern over time: Day 8 there was increased αGST, μGST and albumin; on Day 15 increased clusterin, albumin and Kim-1. In summary, HDN altered the newer and more sensitive renal biomarkers in a time and possibly compound dependent manner. 相似文献
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炎性肠病活动性的分子标志物 总被引:9,自引:6,他引:3
炎性肠病(inflammatory bowel disease,IBD)包括两个重要的肠病:溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD).IBD活动性的评估结果可指导临床制定治疗方案。现在临床上多采用复合指标进行评估,如:CD活动性指标、IBD研究国际分类法等。胃肠病学者希望能找到一个IBD活动性的分子标志物,有足够的特异性和灵敏度并易于监测。 1 抗体的检测 1.1 抗中性粒细胞胞质IgG抗体抗中性粒细胞胞质IgG抗体(antineutropil cytoplasmic IgG antibody,ANCA)是粒细胞特有的,最早见于血管炎,尤Wegener肉芽肿病多见,免疫荧光染色呈弥漫性胞质染色,后发现UC患者核旁ANCA染色带 相似文献
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