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排序方式: 共有342条查询结果,搜索用时 156 毫秒
281.
282.
UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development 总被引:2,自引:0,他引:2
Agger K Cloos PA Christensen J Pasini D Rose S Rappsilber J Issaeva I Canaani E Salcini AE Helin K 《Nature》2007,449(7163):731-734
283.
The origin and evolution of the Moon remain controversial, with one of the most important questions for lunar evolution being the timing and duration of basaltic (mare) magmatism. Here we report the result of ion microprobe U-Pb dating of phosphates in a lunar meteorite, Kalahari 009, which is classified as a very-low-Ti mare-basalt breccia. In situ analyses of five phosphate grains, associated with basaltic clasts, give an age of 4.35 +/- 0.15 billion years. These ancient phosphate ages are thought to represent the crystallization ages of parental basalt magma, making Kalahari 009 one of the oldest known mare basalts. We suggest that mare basalt volcanism on the Moon started as early as 4.35 Gyr ago, relatively soon after its formation and differentiation, and preceding the bulk of lunar volcanism which ensued after the late heavy bombardment around 3.8-3.9 Gyr (refs 7 and 8). Considering the extremely low abundances of incompatible elements such as thorium and the rare earth elements in Kalahari 009 (ref. 9) and recent remote-sensing observations illustrating that the cryptomaria tend to be of very-low-Ti basalt type, we conclude that Kalahari 009 is our first sample of a very-low-Ti cryptomare from the Moon. 相似文献
284.
Choudhury AR Ju Z Djojosubroto MW Schienke A Lechel A Schaetzlein S Jiang H Stepczynska A Wang C Buer J Lee HW von Zglinicki T Ganser A Schirmacher P Nakauchi H Rudolph KL 《Nature genetics》2007,39(1):99-105
Telomere shortening limits the proliferative lifespan of human cells by activation of DNA damage pathways, including upregulation of the cell cycle inhibitor p21 (encoded by Cdkn1a, also known as Cip1 and Waf1)) (refs. 1-5). Telomere shortening in response to mutation of the gene encoding telomerase is associated with impaired organ maintenance and shortened lifespan in humans and in mice. The in vivo function of p21 in the context of telomere dysfunction is unknown. Here we show that deletion of p21 prolongs the lifespan of telomerase-deficient mice with dysfunctional telomeres. p21 deletion improved hematolymphopoiesis and the maintenance of intestinal epithelia without rescuing telomere function. Moreover, deletion of p21 rescued proliferation of intestinal progenitor cells and improved the repopulation capacity and self-renewal of hematopoietic stem cells from mice with dysfunctional telomeres. In these mice, apoptotic responses remained intact, and p21 deletion did not accelerate chromosomal instability or cancer formation. This study provides experimental evidence that telomere dysfunction induces p21-dependent checkpoints in vivo that can limit longevity at the organismal level. 相似文献
285.
286.
A common genetic risk factor for colorectal and prostate cancer 总被引:14,自引:0,他引:14
Haiman CA Le Marchand L Yamamato J Stram DO Sheng X Kolonel LN Wu AH Reich D Henderson BE 《Nature genetics》2007,39(8):954-956
Variants on chromosome 8q24 contribute risk for prostate cancer; here, we tested whether they also modulate risk for colorectal cancer. We studied 1,807 affected individuals and 5,511 controls and found that one variant, rs6983267, is also significantly associated with colorectal cancer (odds ratio = 1.22; P = 4.4 x 10(-6)) and that the apportionment of risk among the variants differs significantly between the two cancers. Comprehensive testing in the region uncovered variants capturing significant additional risk. Our results show that variants at 8q24 have different effects on cancer development that depend on the tissue type. 相似文献
287.
Richards A van den Maagdenberg AM Jen JC Kavanagh D Bertram P Spitzer D Liszewski MK Barilla-Labarca ML Terwindt GM Kasai Y McLellan M Grand MG Vanmolkot KR de Vries B Wan J Kane MJ Mamsa H Schäfer R Stam AH Haan J de Jong PT Storimans CW van Schooneveld MJ Oosterhuis JA Gschwendter A Dichgans M Kotschet KE Hodgkinson S Hardy TA Delatycki MB Hajj-Ali RA Kothari PH Nelson SF Frants RR Baloh RW Ferrari MD Atkinson JP 《Nature genetics》2007,39(9):1068-1070
Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle-age onset. In nine families, we identified heterozygous C-terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias. 相似文献
288.
Crow YJ Leitch A Hayward BE Garner A Parmar R Griffith E Ali M Semple C Aicardi J Babul-Hirji R Baumann C Baxter P Bertini E Chandler KE Chitayat D Cau D Déry C Fazzi E Goizet C King MD Klepper J Lacombe D Lanzi G Lyall H Martínez-Frías ML Mathieu M McKeown C Monier A Oade Y Quarrell OW Rittey CD Rogers RC Sanchis A Stephenson JB Tacke U Till M Tolmie JL Tomlin P Voit T Weschke B Woods CG Lebon P Bonthron DT Ponting CP Jackson AP 《Nature genetics》2006,38(8):910-916
Aicardi-Goutières syndrome (AGS) is an autosomal recessive neurological disorder, the clinical and immunological features of which parallel those of congenital viral infection. Here we define the composition of the human ribonuclease H2 enzyme complex and show that AGS can result from mutations in the genes encoding any one of its three subunits. Our findings demonstrate a role for ribonuclease H in human neurological disease and suggest an unanticipated relationship between ribonuclease H2 and the antiviral immune response that warrants further investigation. 相似文献
289.
Emanuela Talamonti Anna M. Pauter Abolfazl Asadi Alexander W. Fischer Valerio Chiurchiù Anders Jacobsson 《Cellular and molecular life sciences : CMLS》2017,74(15):2815-2826
Docosahexaenoic acid (DHA) is an omega-3 fatty acid obtained from the diet or synthesized from alpha-linolenic acid through the action of fatty acid elongases (ELOVL) and desaturases. DHA plays important roles in the central nervous system as well as in peripheral organs and is the precursor of several molecules that regulate resolution of inflammation. In the present study, we questioned whether impaired synthesis of DHA affected macrophage plasticity and polarization both in vitro and in vivo models. For this we investigated the activation status and inflammatory response of bone marrow-derived M1 and M2 macrophages obtained from mice deficient of Elovl2 (Elovl2?/?), a key enzyme for DHA synthesis in mammals. Although both wild type and Elovl2?/? mice were able to generate efficient M1 and M2 macrophages, M1 cells derived from Elovl2?/? mice showed an increased expression of key markers (iNOS, CD86 and MARCO) and cytokines (IL-6, IL-12 and IL-23). However, M2 macrophages exhibited upregulated M1-like markers like CD80, CD86 and IL-6, concomitantly with a downregulation of their signature marker CD206. These effects were counteracted in cells obtained from DHA-supplemented animals. Finally, white adipose tissue of Elovl2?/? mice presented an M1-like pro-inflammatory phenotype. Hence, impairment of systemic DHA synthesis delineates an alteration of M1/M2 macrophages both in vitro and in vivo, with M1 being hyperactive and more pro-inflammatory while M2 less protective, supporting the view that DHA has a key role in controlling the balance between pro- and anti-inflammatory processes. 相似文献