全文获取类型
收费全文 | 1027篇 |
免费 | 43篇 |
国内免费 | 72篇 |
出版年
2022年 | 7篇 |
2021年 | 21篇 |
2020年 | 5篇 |
2018年 | 5篇 |
2017年 | 10篇 |
2016年 | 29篇 |
2015年 | 69篇 |
2014年 | 46篇 |
2013年 | 47篇 |
2012年 | 86篇 |
2011年 | 140篇 |
2010年 | 94篇 |
2009年 | 32篇 |
2008年 | 32篇 |
2007年 | 35篇 |
2006年 | 15篇 |
2005年 | 68篇 |
2004年 | 69篇 |
2003年 | 39篇 |
2002年 | 22篇 |
2001年 | 30篇 |
2000年 | 8篇 |
1999年 | 7篇 |
1998年 | 4篇 |
1997年 | 16篇 |
1996年 | 13篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 37篇 |
1992年 | 19篇 |
1991年 | 6篇 |
1990年 | 18篇 |
1989年 | 10篇 |
1988年 | 14篇 |
1987年 | 10篇 |
1986年 | 15篇 |
1985年 | 9篇 |
1972年 | 2篇 |
1971年 | 3篇 |
1957年 | 6篇 |
1955年 | 4篇 |
1954年 | 2篇 |
1948年 | 1篇 |
1943年 | 2篇 |
1941年 | 1篇 |
1925年 | 1篇 |
1924年 | 1篇 |
1923年 | 3篇 |
1917年 | 1篇 |
1904年 | 1篇 |
排序方式: 共有1142条查询结果,搜索用时 31 毫秒
81.
T. Nguyen-Dumont M. Mahmoodi F. Hammet T. Tran H. Tsimiklis Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer G.G. Giles J.L. Hopper Australian Breast Cancer Family Registry M.C. Southey D.J. Park 《Analytical biochemistry》2015
Many genetic epidemiology resources have collected dried blood spots (predominantly as Guthrie Cards) as an economical and efficient means of archiving sources of DNA, conferring great value to genetic screening methods that are compatible with this medium. We applied Hi-Plex to screen the breast cancer predisposition gene PALB2 in 93 Guthrie Card-derived DNA specimens previously characterized for PALB2 genetic variants via DNA derived from lymphoblastoid cell lines, whole blood, and buffy coat. Of the 93 archival Guthrie Card-derived DNAs, 92 (99%) were processed successfully and sequenced using approximately half of a MiSeq run. From these 92 DNAs, all 59 known variants were detected and no false-positive variant calls were yielded. Fully 98.13% of amplicons (5417/5520) were represented within 15-fold of the median coverage (2786 reads), and 99.98% of amplicons (5519/5520) were represented at a depth of 10 read-pairs or greater. With Hi-Plex, we show for the first time that a High-Plex amplicon-based massively parallel sequencing (MPS) system can be applied effectively to DNA prepared from dried blood spot archival specimens and, as such, can dramatically increase the scopes of both method and resource. 相似文献
82.
Lisa Langsetmo Tuan V. Nguyen Nguyen D. Nguyen Christopher S. Kovacs Jerilynn C. Prior Jacqueline R. Center Suzanne Morin Robert G. Josse Jonathan D. Adachi David A. Hanley John A. Eisman the Canadian Multicentre Osteoporosis Study Research Group 《CMAJ》2011,183(2):E107-E114
Background
A set of nomograms based on the Dubbo Osteoporosis Epidemiology Study predicts the five- and ten-year absolute risk of fracture using age, bone mineral density and history of falls and low-trauma fracture. We assessed the discrimination and calibration of these nomograms among participants in the Canadian Multicentre Osteoporosis Study.Methods
We included participants aged 55–95 years for whom bone mineral density measurement data and at least one year of follow-up data were available. Self-reported incident fractures were identified by yearly postal questionnaire or interview (years 3, 5 and 10). We included low-trauma fractures before year 10, except those of the skull, face, hands, ankles and feet. We used a Cox proportional hazards model.Results
Among 4152 women, there were 583 fractures, with a mean follow-up time of 8.6 years. Among 1606 men, there were 116 fractures, with a mean follow-up time of 8.3 years. Increasing age, lower bone mineral density, prior fracture and prior falls were associated with increased risk of fracture. For low-trauma fractures, the concordance between predicted risk and fracture events (Harrell C) was 0.69 among women and 0.70 among men. For hip fractures, the concordance was 0.80 among women and 0.85 among men. The observed fracture risk was similar to the predicted risk in all quintiles of risk except the highest quintile of women, where it was lower. The net reclassification index (19.2%, 95% confidence interval [CI] 6.3% to 32.2%), favours the Dubbo nomogram over the current Canadian guidelines for men.Interpretation
The published nomograms provide good fracture-risk discrimination in a representative sample of the Canadian population.Current recommendations for the treatment of osteoporosis are in transition. The T-score-based definition of osteoporosis and osteopenia by the expert committee of the World Health Organization on bone mineral density has been used in many guidelines to set intervention thresholds for treatment. However, studies have consistently reported that the highest number of fractures in a given population occurs in those with osteopenic or normal bone mineral density.1,2 In fact, the National Osteoporosis Foundation has singled out people with osteopenic bone mineral density as a population in which assessment for fracture risk is merited.3Nevertheless, appropriate prevention and treatment strategies for such people are uncertain.4 Recent developments include the assessment of absolute fracture risk based on bone mineral density and other risk factors. Current Canadian methodology determines categorical risk based on age, sex, T-score, fracture history and glucocorticoid use.5 These criteria were derived from Swedish data, but have been assessed and validated in a cohort of Manitoba women.6 Newer nomograms based on the Australian cohort of the Dubbo Osteoporosis Epidemiology Study7 are now available for the calculation of low-trauma hip fracture8 and any fracture.9 These nomograms provide continuous estimates for five- and 10-year absolute fracture risk in both men and women (available at http://fractureriskcalculator.com). The use of factors in addition to bone mineral density may provide a better assessment of fracture risk for people who are near the T-score thresholds and facilitate decisions regarding therapeutic intervention.A key step in the development of any prediction model is the assessment of its validity.10 The aim of our study was to assess the performance of the Australian-derived nomogram among community-dwelling Canadians aged 55–95 years old. The first part of this assessment was a comparison of the nomogram model using the same variables, but using data from a Canadian population — participants in the Canadian Multicentre Osteoporosis Study (www.camos.org). The second part involved computing the calibration and discrimination of the nomogram in a Canadian cohort. The final part was comparison of the new assessments with the existing Canadian risk classification system. 相似文献83.
84.
85.
编码核层蛋白A(lamin A)的LMNA基因突变导致法尼基化的核层蛋白A前体(prelamin A)不能被进一步加工成成熟的核层蛋白A,从而导致一种Hutchinson-Gilford早老症综合征(Hutchinson-Gilford progeria syndrome,HGPS)。一种更严重的早老症——限制性皮肤病(restrictive dermopathy,RD),是由于缺失核层蛋白A前体加工过程中的剪切酶ZMPSTE24引起的。ZMPSTE24的缺失阻止了法尼基化的核层蛋白A前体不能正常加工成为成熟的核层蛋白A,同时导致法尼基化的核层蛋白A前体的堆积。在HGPS和RD病人的成纤维细胞中,发现法尼基化的核层蛋白A前体都定位在核膜,从而影响细胞核膜的完整性,并导致细胞核形的异常,进而导致衰老。最近研究表明经过法尼基酰转移酶抑制剂(farnesyltransferase inhibitor,FTI)处理后的细胞的核形异常减少。同时,FTI能够改善HGPS和RD小鼠的早老症状。本文就核层蛋白A前体的法尼基化对衰老的影响有关研究进展作一综述。 相似文献
86.
87.
西藏台错TT-1剖面厚369 cm,为一套碳酸盐粘土和粘土碳酸盐沉积,地层测年为41.4-4.5 ka,含丰富的轮藻化石,分属于11个轮藻植物群,群落所在地层的碳酸盐和钙质含量分别为80%和33%.从老到新(剖面自下而上):①41.4-26.64 ka(369-319 cm),处于末次冰期间冰阶MIS3a暖期,湖区气候... 相似文献
88.
结直肠癌的多步骤演进模式一直是肿瘤研究的经典,在这一过程中,序贯发生的基因突变(或其它遗传事件)是重要的推动力。本文综述了在结直肠癌中检测到的基因突变情况,并分析了在新一代测序技术的带动下,结直肠癌基因组学的最新进展。结直肠癌组织基因突变的地形图理念对于今后的肿瘤分子诊疗将具有重要意义。肿瘤不仅是基因病,更是信号通路异常病。 相似文献
89.
光学分子影像技术及其在药物研发领域的应用 总被引:2,自引:0,他引:2
光学分子影像技术是一种发展迅速的生物医学影像技术,能够利用生物发光技术或荧光蛋白等,对生物体内特定的生物过程进行无创的定性或定量研究。应用该技术可以对药物进行筛选,选取具有潜在治疗效果的药物进行后续研究,而终止对可能无效药物的研究,同时可以评价药物对肿瘤的代谢、增殖、血管形成、凋亡和组织乏氧等方面的影响。本文主要介绍光学分子影像技术及其在药物研发,尤其是抗肿瘤药物研发领域的应用。 相似文献
90.
Schelonka RL Maheshwari A Carlo WA Taylor S Hansen NI Schendel DE Thorsen P Skogstrand K Hougaard DM Higgins RD;NICHD Neonatal Research Network 《Cytokine》2011,53(2):249-255
Cytokines mediate the host immune response to infectious micro-organisms. The objective of this study was to determine whether immune regulatory interleukins (IL-4, IL-5, IL-6, and IL-10) and inflammatory cytokines (Interferon-γ [INF-γ], tumor necrosis factor-β [TNF-β], IL-2, and IL-17) are associated with an increased risk of developing blood stream bacterial/fungal infection (BSI) in extremely low birth weight (ELBW) infants. ELBW infants from 17 NICHD Neonatal Research Network centers without early onset sepsis were studied. Cytokines were measured from blood on days 1, 3, 7, 14, and 21 after birth. 996 ELBW infants contributed a minimum of 4080 unique measurements for each cytokine during the five sampling periods. Infants with BSI had lower levels of the inflammatory cytokines IL-17 (p=0.01), and higher levels of the regulatory cytokines, IL-6 (p=0.01) and IL-10 (p<0.001). Higher levels of regulatory cytokines relative to pro-inflammatory cytokines were associated with increased risk of BSI even after adjusting for confounding variables. In ELBW infants, the ratio of immune regulatory cytokines to inflammatory cytokines was associated with development of BSI. Altered maturation of regulatory and inflammatory cytokines may increase the risk of serious infection in this population. 相似文献