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排序方式: 共有101条查询结果,搜索用时 15 毫秒
71.
Schwickert TA Lindquist RL Shakhar G Livshits G Skokos D Kosco-Vilbois MH Dustin ML Nussenzweig MC 《Nature》2007,446(7131):83-87
Germinal centres are specialized structures wherein B lymphocytes undergo clonal expansion, class switch recombination, antibody gene diversification and affinity maturation. Three to four antigen-specific B cells colonize a follicle to establish a germinal centre and become rapidly dividing germinal-centre centroblasts that give rise to dark zones. Centroblasts produce non-proliferating centrocytes that are thought to migrate to the light zone of the germinal centre, which is rich in antigen-trapping follicular dendritic cells and CD4+ T cells. It has been proposed that centrocytes are selected in the light zone on the basis of their ability to bind cognate antigen. However, there have been no studies of germinal-centre dynamics or the migratory behaviour of germinal-centre cells in vivo. Here we report the direct visualization of B cells in lymph node germinal centres by two-photon laser-scanning microscopy in mice. Nearly all antigen-specific B cells participating in a germinal-centre reaction were motile and physically restricted to the germinal centre but migrated bi-directionally between dark and light zones. Notably, follicular B cells were frequent visitors to the germinal-centre compartment, suggesting that all B cells scan antigen trapped in germinal centres. Consistent with this observation, we found that high-affinity antigen-specific B cells can be recruited to an ongoing germinal-centre reaction. We conclude that the open structure of germinal centres enhances competition and ensures that rare high-affinity B cells can participate in antibody responses. 相似文献
72.
73.
Schormair B Kemlink D Roeske D Eckstein G Xiong L Lichtner P Ripke S Trenkwalder C Zimprich A Stiasny-Kolster K Oertel W Bachmann CG Paulus W Högl B Frauscher B Gschliesser V Poewe W Peglau I Vodicka P Vávrová J Sonka K Nevsimalova S Montplaisir J Turecki G Rouleau G Gieger C Illig T Wichmann HE Holsboer F Müller-Myhsok B Meitinger T Winkelmann J 《Nature genetics》2008,40(8):946-948
We identified association of restless legs syndrome (RLS) with PTPRD at 9p23-24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5' UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4626664, P(nominal/lambda corrected) = 5.91 x 10(-10), odds ratio (OR) = 1.44; rs1975197, P(nominal/lambda corrected) = 5.81 x 10(-9), OR = 1.31). This work identifies PTPRD as the fourth genome-wide significant locus for RLS. 相似文献
74.
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
75.
Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions 总被引:10,自引:0,他引:10
Winkelmann J Schormair B Lichtner P Ripke S Xiong L Jalilzadeh S Fulda S Pütz B Eckstein G Hauk S Trenkwalder C Zimprich A Stiasny-Kolster K Oertel W Bachmann CG Paulus W Peglau I Eisensehr I Montplaisir J Turecki G Rouleau G Gieger C Illig T Wichmann HE Holsboer F Müller-Myhsok B Meitinger T 《Nature genetics》2007,39(8):1000-1006
76.
Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans 总被引:10,自引:0,他引:10
Murdoch S Djuric U Mazhar B Seoud M Khan R Kuick R Bagga R Kircheisen R Ao A Ratti B Hanash S Rouleau GA Slim R 《Nature genetics》2006,38(3):300-302
Hydatidiform mole (HM) is an abnormal human pregnancy with no embryo and cystic degeneration of placental villi. We report five mutations in the maternal gene NALP7 in individuals with familial and recurrent HMs. NALP7 is a member of the CATERPILLER protein family involved in inflammation and apoptosis. NALP7 is the first maternal effect gene identified in humans and is also responsible for recurrent spontaneous abortions, stillbirths and intrauterine growth retardation. 相似文献
77.
滑动型颈椎前路固定板在骨科临床上得到逐步应用,以取代限制型固定板并用来承担椎体上载荷及防止植骨下沉。然而,目前骨科临床对两种前路固定板的综合生物力学性能评价很少。研究使用18具猪颈椎骨模拟椎体切除手术,使用MTSMini858实验台模拟人体颈椎生理运动,采用三维运动分析系统、微型压力传感器分别测定椎体运动及椎间压力,实验评价滑动型与限制型前路固定板的生物力学性能。实验数据表明,滑动型固定板在两节段椎体次全切除术中的综合生物力学特性优于限制型前路固定板。 相似文献
78.
79.
Eeles RA Kote-Jarai Z Giles GG Olama AA Guy M Jugurnauth SK Mulholland S Leongamornlert DA Edwards SM Morrison J Field HI Southey MC Severi G Donovan JL Hamdy FC Dearnaley DP Muir KR Smith C Bagnato M Ardern-Jones AT Hall AL O'Brien LT Gehr-Swain BN Wilkinson RA Cox A Lewis S Brown PM Jhavar SG Tymrakiewicz M Lophatananon A Bryant SL;UK Genetic Prostate Cancer Study Collaborators;British Association of Urological Surgeons' Section of Oncology;UK ProtecT Study Collaborators Horwich A Huddart RA 《Nature genetics》2008,40(3):316-321
Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at =60 years or with a family history of disease, and 1,894 population-screened controls with a low prostate-specific antigen (PSA) concentration (<0.5 ng/ml). We analyzed these samples for 541,129 SNPs using the Illumina Infinium platform. Initial putative associations were confirmed using a further 3,268 cases and 3,366 controls. We identified seven loci associated with prostate cancer on chromosomes 3, 6, 7, 10, 11, 19 and X (P = 2.7 x 10(-8) to P = 8.7 x 10(-29)). We confirmed previous reports of common loci associated with prostate cancer at 8q24 and 17q. Moreover, we found that three of the newly identified loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK3. 相似文献
80.
Merveille AC Davis EE Becker-Heck A Legendre M Amirav I Bataille G Belmont J Beydon N Billen F Clément A Clercx C Coste A Crosbie R de Blic J Deleuze S Duquesnoy P Escalier D Escudier E Fliegauf M Horvath J Hill K Jorissen M Just J Kispert A Lathrop M Loges NT Marthin JK Momozawa Y Montantin G Nielsen KG Olbrich H Papon JF Rayet I Roger G Schmidts M Tenreiro H Towbin JA Zelenika D Zentgraf H Georges M Lequarré AS Katsanis N Omran H Amselem S 《Nature genetics》2011,43(1):72-78
Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex. 相似文献