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251.
Wain LV Verwoert GC O'Reilly PF Shi G Johnson T Johnson AD Bochud M Rice KM Henneman P Smith AV Ehret GB Amin N Larson MG Mooser V Hadley D Dörr M Bis JC Aspelund T Esko T Janssens AC Zhao JH Heath S Laan M Fu J Pistis G Luan J Arora P Lucas G Pirastu N Pichler I Jackson AU Webster RJ Zhang F Peden JF Schmidt H Tanaka T Campbell H Igl W Milaneschi Y Hottenga JJ Vitart V Chasman DI Trompet S Bragg-Gresham JL Alizadeh BZ Chambers JC Guo X Lehtimäki T Kühnel B Lopez LM Polašek O Boban M Nelson CP 《Nature genetics》2011,43(10):1005-1011
Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP. 相似文献
252.
Xu B Roos JL Dexheimer P Boone B Plummer B Levy S Gogos JA Karayiorgou M 《Nature genetics》2011,43(9):864-868
Despite its high heritability, a large fraction of individuals with schizophrenia do not have a family history of the disease (sporadic cases). Here we examined the possibility that rare de novo protein-altering mutations contribute to the genetic component of schizophrenia by sequencing the exomes of 53 sporadic cases, 22 unaffected controls and their parents. We identified 40 de novo mutations in 27 cases affecting 40 genes, including a potentially disruptive mutation in DGCR2, a gene located in the schizophrenia-predisposing 22q11.2 microdeletion region. A comparison to rare inherited variants indicated that the identified de novo mutations show a large excess of non-synonymous changes in schizophrenia cases, as well as a greater potential to affect protein structure and function. Our analyses suggest a major role for de novo mutations in schizophrenia as well as a large mutational target, which together provide a plausible explanation for the high global incidence and persistence of the disease. 相似文献
253.
Sanna S Jackson AU Nagaraja R Willer CJ Chen WM Bonnycastle LL Shen H Timpson N Lettre G Usala G Chines PS Stringham HM Scott LJ Dei M Lai S Albai G Crisponi L Naitza S Doheny KF Pugh EW Ben-Shlomo Y Ebrahim S Lawlor DA Bergman RN Watanabe RM Uda M Tuomilehto J Coresh J Hirschhorn JN Shuldiner AR Schlessinger D Collins FS Davey Smith G Boerwinkle E Cao A Boehnke M Abecasis GR Mohlke KL 《Nature genetics》2008,40(2):198-203
254.
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
255.
A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis 总被引:1,自引:0,他引:1
Khor CC Chapman SJ Vannberg FO Dunne A Murphy C Ling EY Frodsham AJ Walley AJ Kyrieleis O Khan A Aucan C Segal S Moore CE Knox K Campbell SJ Lienhardt C Scott A Aaby P Sow OY Grignani RT Sillah J Sirugo G Peshu N Williams TN Maitland K Davies RJ Kwiatkowski DP Day NP Yala D Crook DW Marsh K Berkley JA O'Neill LA Hill AV 《Nature genetics》2007,39(4):523-528
Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction. 相似文献
256.
Arterial thrombosis is the single most common cause of death and disability in industrialized societies and is the primary
pathogenic mechanism underlying acute myocardial infarction and ischemic stroke. Platelets play a central role in this process,
and as a consequence, a great deal of effort has gone into identifying the mechanisms regulating the adhesive function of
platelets. Platelet adhesion is controlled by intracellular signaling pathways, with growing evidence for a major role for
phosphoinositide 3-kinases (PI3Ks) in this process. Platelets express all type I PI3K isoforms, including p110α, p110β, p110δ
and p110γ, with recent evidence suggesting important roles for p110γ and p110β in regulating distinct phases of the platelet
activation process. Deficiency of p110 γ or inhibition of p110β produces a marked defect in arterial thrombosis without a
corresponding increase in bleeding time, raising the possibility that inhibition of one or more PI3K isoforms may represent
an effective antithrombotic approach.
Received 3 January 2006; received after revision 20 February 2006; accepted 20 February 2006 相似文献
257.
吴雄武 《南京工业大学学报(自然科学版)》2006,28(1)
采用新近提出的迷向周期和方法(IPS),结合自导Lang evin动态模拟,模拟研究9余肽折褶成β簮结构的情况,表明了该结构与NMR观察到的基本一致,而Ewald模拟由于是强烈的镜像相互作用会产生构型偏差,获得致密构型的几率增大,表明IPS方法更适合于周期边界条件的模拟. 相似文献
258.
Estevão Alves-Silva Alexandra Bächtold Gudryan Jackson Barônio Helena Maura Torezan-Silingardi Kleber Del-Claro 《Journal of Natural History》2015,49(13-14):841-851
Extrafloral nectary drinking ants are known as effective plant guards, but some herbivores may circumvent ant attacks by foraging on different plant parts or presenting adaptations to avoid ant predation. Here we experimentally investigated the effect of Camponotus blandus on the florivory of the extrafloral nectaried shrub Banisteriopsis malifolia; and a possible spatial segregation between ants and herbivores (leaves and flowers). Flower buds are attacked by Anthonomus weevils. Results revealed no significant influence of C. blandus on the reduction of florivory. Adult Anthonomus are hard-bodied and were immune to ant bites; larvae are endophytic, so protected from ants. Ants and adult beetles were concentrated in different plant parts (leaves and flowers, respectively) so restraining the probability of encounters. Our results indicate that the system C. blandus–Anthonomus–B. malifolia is not stable, as ants receive extrafloral nectar, but are unable to protect the plant against weevils. 相似文献
259.
As part of the 2001 Census, the One Number Census project estimated and adjusted the Census database for underenumeration. As a result of the highly innovative One Number Census and the Quality Assurance process it encompassed, it was also ensured that robust results could be obtained for each local authority area. This article examines some of the issues and analyses that were undertaken as part of that assessment of the 2001 Census population counts for England and Wales. The article firstly highlights the key issues surrounding the implementation of the 2001 Census fieldwork. The article then explores the 2001 Census results through a series of demographic analyses to illustrate the sorts of issues investigated during the One Number Census Quality Assurance process itself. These analyses look at the patterns contained within the results, and comparisons with key alternative sources of population counts. Overall, these in-depth analyses and investigations provide further credence to the plausibility of the One Number Census results. 相似文献
260.
The composition of four radiocarbon-dated, late Pleistocene woodrat middens is reported and analyzed. A date of 11,850 ±550 BP records the first reported macrofossil occurrence in this region of late Pleistocene Pinus monophylla-Juniperus osteosperma woodlands. A 7,800 ±350 BP date documents the most recent J. osteosperma woodlands in this presently coniferless desert area, while a date of 12,100 ±400 BP is the oldest record of juniper woodlands among the four middens. Other juniper and creosote bush desert flora radiocarbon dates along with six pollen profiles were obtained. The research suggests that as recently as 7,800 BP this part of the Mohave Desert was subject to a cooler, moister climate than at present, and that the aboriginal food resources of pinyon seeds and juniper berries were probably available to early prehistoric man in this area. 相似文献