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51.
Nejentsev S Howson JM Walker NM Szeszko J Field SF Stevens HE Reynolds P Hardy M King E Masters J Hulme J Maier LM Smyth D Bailey R Cooper JD Ribas G Campbell RD Clayton DG Todd JA;Wellcome Trust Case Control Consortium 《Nature》2007,450(7171):887-892
The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods-recursive partitioning and regression-to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; P(combined) = 2.01 x 10(-19) and 2.35 x 10(-13), respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. 相似文献
52.
Steinhauser ML Bailey AP Senyo SE Guillermier C Perlstein TS Gould AP Lee RT Lechene CP 《Nature》2012,481(7382):516-519
Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter, but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with submicrometre resolution. Here we apply MIMS to diverse organisms, including Drosophila, mice and humans. We test the 'immortal strand hypothesis', which predicts that during asymmetric stem cell division chromosomes containing older template DNA are segregated to the daughter destined to remain a stem cell, thus insuring lifetime genetic stability. After labelling mice with (15)N-thymidine from gestation until post-natal week 8, we find no (15)N label retention by dividing small intestinal crypt cells after a four-week chase. In adult mice administered (15)N-thymidine pulse-chase, we find that proliferating crypt cells dilute the (15)N label, consistent with random strand segregation. We demonstrate the broad utility of MIMS with proof-of-principle studies of lipid turnover in Drosophila and translation to the human haematopoietic system. These studies show that MIMS provides high-resolution quantification of stable isotope labels that cannot be obtained using other techniques and that is broadly applicable to biological and medical research. 相似文献
53.
54.
Mungall AJ Palmer SA Sims SK Edwards CA Ashurst JL Wilming L Jones MC Horton R Hunt SE Scott CE Gilbert JG Clamp ME Bethel G Milne S Ainscough R Almeida JP Ambrose KD Andrews TD Ashwell RI Babbage AK Bagguley CL Bailey J Banerjee R Barker DJ Barlow KF Bates K Beare DM Beasley H Beasley O Bird CP Blakey S Bray-Allen S Brook J Brown AJ Brown JY Burford DC Burrill W Burton J Carder C Carter NP Chapman JC Clark SY Clark G Clee CM Clegg S Cobley V Collier RE Collins JE Colman LK Corby NR Coville GJ 《Nature》2003,425(6960):805-811
55.
贾巍巍 《山西师范大学学报:自然科学版》2004,18(3):6-11
本文讨论F4上n维线性空间的k维子空间W,这些子空间都有特定的自同构群(实际上是典型群GLn(F4)的一个子群),根据群中元素形式的不同可将子空间W分为两类,并对寻找n维空间中形如这两类的n/2维自对偶子空间提供了一种采用降低维数寻找的方法。 相似文献
56.
孤岛油田馆(1 2)砂层组属于河流相沉积,其纵向、横向相变迅速,砂体难以大面积追踪,本利用河流结构单元分析法、标准层与辅助标志层控制下的“旋回-厚度”对比法,很好地解决了馆(1 2)地层的划分对比问题,其中馆(1 2)砂层组内辅助标志层的发现为地层的划分对比提供了重要的保证.根据结构单元分析、砂体的岩性特征、粒度特征、河流砂体的空间展布形态以及河流曲率的计算,对馆(1 2)河流沉积的垂向旋回性及沉积模式进行了研究。对比Miall的16种河流分类方案,孤岛油田馆(1 2)砂层组属于细粒曲流河沉积. 相似文献
57.
图像分割是一种重要的图像分析技术,它不仅得到人们广泛的重视和研究,也在实际中得到大量的应用。本文针对一些经典分割算法对多梯度复杂图像分割边缘定位不准确,易受噪声干扰的特点,提出了一种利用图像边缘区域对多梯度复杂图像进行自适应阈值分割的算法。通过对各种算法的比较,本算法抗干扰能力较强,稳定性好,而且完全自动,不需预先设定任何参数。对多种图像的实验表明本文方法十分有效。 相似文献
58.
K. D. Bailey 《Systemic Practice and Action Research》1990,3(4):365-382
Social Entropy Theory (SET) is a very general macrosociological systems theory. The present paper is an overview which presents selected salient features of the larger model. Special attention is given to the specification of macrosociological variables which can serve as social indicators in a comparative framework of societal development. First, the goals of the SET model are stated. Then the basic model is sketched, and entropy is discussed as a measure of system state. Attention then turns to the specification of a holistic set of macrosociological systems variables. By seeking all correlates of the level (L), six salient global components are developed. These are population (P), information (I), spatial area (S), technology (T), organization (O), and level of living (L). This PISTOL (or PILOTS) model seems to be exhaustive and forms a comparative framework (when suitable indicators are specified for all components) for the analysis of social systems at all levels of development. A distinction is made among global, mutable, and immutable properties. 相似文献
59.
Di Bernardo MC Crowther-Swanepoel D Broderick P Webb E Sellick G Wild R Sullivan K Vijayakrishnan J Wang Y Pittman AM Sunter NJ Hall AG Dyer MJ Matutes E Dearden C Mainou-Fowler T Jackson GH Summerfield G Harris RJ Pettitt AR Hillmen P Allsup DJ Bailey JR Pratt G Pepper C Fegan C Allan JM Catovsky D Houlston RS 《Nature genetics》2008,40(10):1204-1210
We conducted a genome-wide association study of 299,983 tagging SNPs for chronic lymphocytic leukemia (CLL) and performed validation in two additional series totaling 1,529 cases and 3,115 controls. We identified six previously unreported CLL risk loci at 2q13 (rs17483466; P = 2.36 x 10(-10)), 2q37.1 (rs13397985, SP140; P = 5.40 x 10(-10)), 6p25.3 (rs872071, IRF4; P = 1.91 x 10(-20)), 11q24.1 (rs735665; P = 3.78 x 10(-12)), 15q23 (rs7176508; P = 4.54 x 10(-12)) and 19q13.32 (rs11083846, PRKD2; P = 3.96 x 10(-9)). These data provide the first evidence for the existence of common, low-penetrance susceptibility to a hematological malignancy and new insights into disease causation in CLL. 相似文献
60.
Williams ES Stap J Essers J Ponnaiya B Luijsterburg MS Krawczyk PM Ullrich RL Aten JA Bailey SM 《Nature genetics》2007,39(6):696-8; author reply 698-9