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排序方式: 共有297条查询结果,搜索用时 15 毫秒
201.
Laurie CC Laurie CA Rice K Doheny KF Zelnick LR McHugh CP Ling H Hetrick KN Pugh EW Amos C Wei Q Wang LE Lee JE Barnes KC Hansel NN Mathias R Daley D Beaty TH Scott AF Ruczinski I Scharpf RB Bierut LJ Hartz SM Landi MT Freedman ND Goldin LR Ginsburg D Li J Desch KC Strom SS Blot WJ Signorello LB Ingles SA Chanock SJ Berndt SI Le Marchand L Henderson BE Monroe KR Heit JA de Andrade M Armasu SM Regnier C Lowe WL Hayes MG Marazita ML Feingold E Murray JC Melbye M Feenstra B Kang JH Wiggs JL 《Nature genetics》2012,44(6):642-650
We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18). 相似文献
202.
Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA 总被引:1,自引:0,他引:1
Lindhurst MJ Parker VE Payne F Sapp JC Rudge S Harris J Witkowski AM Zhang Q Groeneveld MP Scott CE Daly A Huson SM Tosi LL Cunningham ML Darling TN Geer J Gucev Z Sutton VR Tziotzios C Dixon AK Helliwell T O'Rahilly S Savage DB Wakelam MJ Barroso I Biesecker LG Semple RK 《Nature genetics》2012,44(8):928-933
The phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway is critical for cellular growth and metabolism. Correspondingly, loss of function of PTEN, a negative regulator of PI3K, or activating mutations in AKT1, AKT2 or AKT3 have been found in distinct disorders featuring overgrowth or hypoglycemia. We performed exome sequencing of DNA from unaffected and affected cells from an individual with an unclassified syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified the cancer-associated mutation encoding p.His1047Leu in PIK3CA, the gene that encodes the p110α catalytic subunit of PI3K, only in affected cells. Sequencing of PIK3CA in ten additional individuals with overlapping syndromes identified either the p.His1047Leu alteration or a second cancer-associated alteration, p.His1047Arg, in nine cases. Affected dermal fibroblasts showed enhanced basal and epidermal growth factor (EGF)-stimulated phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) generation and concomitant activation of downstream signaling relative to their unaffected counterparts. Our findings characterize a distinct overgrowth syndrome, biochemically demonstrate activation of PI3K signaling and thereby identify a rational therapeutic target. 相似文献
203.
Ikram MA Fornage M Smith AV Seshadri S Schmidt R Debette S Vrooman HA Sigurdsson S Ropele S Taal HR Mook-Kanamori DO Coker LH Longstreth WT Niessen WJ DeStefano AL Beiser A Zijdenbos AP Struchalin M Jack CR Rivadeneira F Uitterlinden AG Knopman DS Hartikainen AL Pennell CE Thiering E Steegers EA Hakonarson H Heinrich J Palmer LJ Jarvelin MR McCarthy MI Grant SF St Pourcain B Timpson NJ Smith GD Sovio U;Early Growth Genetics Consortium Nalls MA Au R Hofman A Gudnason H van der Lugt A Harris TB 《Nature genetics》2012,44(5):539-544
During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 × 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 × 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 × 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 × 10(-3) for 6q22 and 1.2 × 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size. 相似文献
204.
Quesada V Conde L Villamor N Ordóñez GR Jares P Bassaganyas L Ramsay AJ Beà S Pinyol M Martínez-Trillos A López-Guerra M Colomer D Navarro A Baumann T Aymerich M Rozman M Delgado J Giné E Hernández JM González-Díaz M Puente DA Velasco G Freije JM Tubío JM Royo R Gelpí JL Orozco M Pisano DG Zamora J Vázquez M Valencia A Himmelbauer H Bayés M Heath S Gut M Gut I Estivill X López-Guillermo A Puente XS Campo E López-Otín C 《Nature genetics》2012,44(1):47-52
Here we perform whole-exome sequencing of samples from 105 individuals with chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in Western countries. We found 1,246 somatic mutations potentially affecting gene function and identified 78 genes with predicted functional alterations in more than one tumor sample. Among these genes, SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7% of affected individuals. Further analysis in 279 individuals with CLL showed that SF3B1 mutations were associated with faster disease progression and poor overall survival. This work provides the first comprehensive catalog of somatic mutations in CLL with relevant clinical correlates and defines a large set of new genes that may drive the development of this common form of leukemia. The results reinforce the idea that targeting several well-known genetic pathways, including mRNA splicing, could be useful in the treatment of CLL and other malignancies. 相似文献
205.
The central nervous system (CNS) is considered an immune-privileged organ that maintains an adaptable immune surveillance
system. Dysregulated immune function within the CNS contributes to the development of brain tumor growth, and robust immune
activation results in excessive inflammation. Human lymphocyte antigen-G (HLA-G) proteins with tolerogenic immunoreactivity
have been implicated in various pathophysiological processes including immune surveillance, governing homeostasis and immune
regulation. In this review, we describe the wealth of evidence for the involvement of HLA-G in the CNS under physiological
and pathological conditions. Further, we review regulatory functions that may be applicable as beneficial strategies in the
therapeutic manipulation of immune-mediated CNS immune responses. Additionally, we try to understand how this molecule cooperates
with other CNS-resident cells to maintain normal immune homeostasis, while still facilitating the development of the appropriate
immune responses. 相似文献
206.
Haiman CA Chen GK Vachon CM Canzian F Dunning A Millikan RC Wang X Ademuyiwa F Ahmed S Ambrosone CB Baglietto L Balleine R Bandera EV Beckmann MW Berg CD Bernstein L Blomqvist C Blot WJ Brauch H Buring JE Carey LA Carpenter JE Chang-Claude J Chanock SJ Chasman DI Clarke CL Cox A Cross SS Deming SL Diasio RB Dimopoulos AM Driver WR Dünnebier T Durcan L Eccles D Edlund CK Ekici AB Fasching PA Feigelson HS Flesch-Janys D Fostira F Försti A Fountzilas G 《Nature genetics》2011,43(12):1210-1214
Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations. 相似文献
207.
Relative overexpression of X-linked genes in mouse embryonic stem cells is consistent with Ohno's hypothesis 总被引:1,自引:0,他引:1
Lin H Halsall JA Antczak P O'Neill LP Falciani F Turner BM 《Nature genetics》2011,43(12):1169-70; author reply 1171-2
208.
The genome of Theobroma cacao 总被引:2,自引:0,他引:2
Argout X Salse J Aury JM Guiltinan MJ Droc G Gouzy J Allegre M Chaparro C Legavre T Maximova SN Abrouk M Murat F Fouet O Poulain J Ruiz M Roguet Y Rodier-Goud M Barbosa-Neto JF Sabot F Kudrna D Ammiraju JS Schuster SC Carlson JE Sallet E Schiex T Dievart A Kramer M Gelley L Shi Z Bérard A Viot C Boccara M Risterucci AM Guignon V Sabau X Axtell MJ Ma Z Zhang Y Brown S Bourge M Golser W Song X Clement D Rivallan R Tahi M Akaza JM Pitollat B Gramacho K D'Hont A Brunel D Infante D Kebe I Costet P 《Nature genetics》2011,43(2):101-108
We sequenced and assembled the draft genome of Theobroma cacao, an economically important tropical-fruit tree crop that is the source of chocolate. This assembly corresponds to 76% of the estimated genome size and contains almost all previously described genes, with 82% of these genes anchored on the 10 T. cacao chromosomes. Analysis of this sequence information highlighted specific expansion of some gene families during evolution, for example, flavonoid-related genes. It also provides a major source of candidate genes for T. cacao improvement. Based on the inferred paleohistory of the T. cacao genome, we propose an evolutionary scenario whereby the ten T. cacao chromosomes were shaped from an ancestor through eleven chromosome fusions. 相似文献
209.
High mutation rates have driven extensive structural polymorphism among human Y chromosomes 总被引:15,自引:0,他引:15
Repping S van Daalen SK Brown LG Korver CM Lange J Marszalek JD Pyntikova T van der Veen F Skaletsky H Page DC Rozen S 《Nature genetics》2006,38(4):463-467
Although much structural polymorphism in the human genome has been catalogued, the kinetics of underlying change remain largely unexplored. Because human Y chromosomes are clonally inherited, it has been possible to capture their detailed relationships in a robust, worldwide genealogical tree. Examination of structural variation across this tree opens avenues for investigating rates of underlying mutations. We selected one Y chromosome from each of 47 branches of this tree and searched for large-scale variation. Four chromosomal regions showed extensive variation resulting from numerous large-scale mutations. Within the tree encompassed by the studied chromosomes, the distal-Yq heterochromatin changed length > or = 12 times, the TSPY gene array changed length > or = 23 times, the 3.6-Mb IR3/IR3 region changed orientation > or = 12 times and the AZFc region was rearranged > or = 20 times. After determining the total time spanned by all branches of this tree (approximately 1.3 million years or 52,000 generations), we converted these mutation counts to lower bounds on rates: > or = 2.3 x 10(-4), > or = 4.4 x 10(-4), > or = 2.3 x 10(-4) and > or = 3.8 x 10(-4) large-scale mutations per father-to-son Y transmission, respectively. Thus, high mutation rates have driven extensive structural polymorphism among human Y chromosomes. At the same time, we found limited variation in the copy number of Y-linked genes, which raises the possibility of selective constraints. 相似文献
210.
Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8 总被引:7,自引:0,他引:7
Moseley ML Zu T Ikeda Y Gao W Mosemiller AK Daughters RS Chen G Weatherspoon MR Clark HB Ebner TJ Day JW Ranum LP 《Nature genetics》2006,38(7):758-769