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排序方式: 共有243条查询结果,搜索用时 15 毫秒
1.
Ting SB Deneault E Hope K Cellot S Chagraoui J Mayotte N Dorn JF Laverdure JP Harvey M Hawkins ED Russell SM Maddox PS Iscove NN Sauvageau G 《Blood》2012,119(11):2510-2522
The stem cell-intrinsic model of self-renewal via asymmetric cell division (ACD) posits that fate determinants be partitioned unequally between daughter cells to either activate or suppress the stemness state. ACD is a purported mechanism by which hematopoietic stem cells (HSCs) self-renew, but definitive evidence for this cellular process remains open to conjecture. To address this issue, we chose 73 candidate genes that function within the cell polarity network to identify potential determinants that may concomitantly alter HSC fate while also exhibiting asymmetric segregation at cell division. Initial gene-expression profiles of polarity candidates showed high and differential expression in both HSCs and leukemia stem cells. Altered HSC fate was assessed by our established in vitro to in vivo screen on a subcohort of candidate polarity genes, which revealed 6 novel positive regulators of HSC function: Ap2a2, Gpsm2, Tmod1, Kif3a, Racgap1, and Ccnb1. Interestingly, live-cell videomicroscopy of the endocytic protein AP2A2 shows instances of asymmetric segregation during HSC/progenitor cell cytokinesis. These results contribute further evidence that ACD is functional in HSC self-renewal, suggest a role for Ap2a2 in HSC activity, and provide a unique opportunity to prospectively analyze progeny from HSC asymmetric divisions. 相似文献
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Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model 总被引:6,自引:2,他引:6
Iwasaki M Kuwata T Yamazaki Y Jenkins NA Copeland NG Osato M Ito Y Kroon E Sauvageau G Nakamura T 《Blood》2005,105(2):784-793
The chromosomal translocation t(7; 11)(p15;p15), observed in human myeloid leukemia, results in a NUP98 and HOXA9 gene fusion. We generated a transgenic mouse line that specifically expressed the chimeric NUP98-HOXA9 gene in the myeloid lineage. While only 20% of the transgenic mice progressed to leukemia after a latency period, myeloid progenitor cells from nonleukemic transgenic mice still exhibited increased proliferative potential. This suggested that the NUP98-HOXA9 fusion induced a preleukemic phase, and other factors were required for complete leukemogenesis. NUP98-HOXA9 expression promoted the onset of retrovirus-induced BXH2 myeloid leukemia. This phenomenon was used to identify cooperative disease genes as common integration sites (CISs). Meis1, a known HOX cofactor, was identified as a CIS with a higher integration frequency in transgenic than in wild-type BXH2 mice. By the same means we identified further 4 candidate cooperative genes, Dnalc4, Fcgr2b, Fcrl, and Con1. These genes cooperated with NUP98-HOXA9 in transforming NIH 3T3 cells. The system described here is a powerful tool to identify cooperative oncogenes and will assist in the clarification of the multistep process of carcinogenesis. 相似文献
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Herault O Hope KJ Deneault E Mayotte N Chagraoui J Wilhelm BT Cellot S Sauvageau M Andrade-Navarro MA Hébert J Sauvageau G 《The Journal of experimental medicine》2012,209(5):895-901
The determinants of normal and leukemic stem cell self-renewal remain poorly characterized. We report that expression of the reactive oxygen species (ROS) scavenger glutathione peroxidase 3 (GPx3) positively correlates with the frequency of leukemia stem cells (LSCs) in Hoxa9+Meis1-induced leukemias. Compared with a leukemia with a low frequency of LSCs, a leukemia with a high frequency of LSCs showed hypomethylation of the Gpx3 promoter region, and expressed high levels of Gpx3 and low levels of ROS. LSCs and normal hematopoietic stem cells (HSCs) engineered to express Gpx3 short hairpin RNA (shRNA) were much less competitive in vivo than control cells. However, progenitor cell proliferation and differentiation was not affected by Gpx3 shRNA. Consistent with this, HSCs overexpressing Gpx3 were significantly more competitive than control cells in long-term repopulation experiments, and overexpression of the self-renewal genes Prdm16 or Hoxb4 boosted Gpx3 expression. In human primary acute myeloid leukemia samples, GPX3 expression level directly correlated with adverse prognostic outcome, revealing a potential novel target for the eradication of LSCs. 相似文献
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Eve Dubé Fannie Defay Vladimir Gilca Julie A Bettinger Chantal Sauvageau France Lavoie François D Boucher Shelly McNeil Ian Gemmill Nicole Boulianne 《BMC public health》2011,11(1):128
Background
In June 2009, the World Health Organization declared an A(H1N1) influenza pandemic. In October 2009, the largest vaccination campaign in Canadian history began. The aim of this study was to document paediatricians' knowledge, attitudes and practices (KAP) regarding A(H1N1) pandemic influenza and its prevention by vaccination just after the beginning of the A(H1N1) vaccination campaign and to compare the results with those obtained before campaign initiation. 相似文献7.
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Ecker RD Guidot CA Hanel RA Wehman JC Sauvageau E Guterman LR Hopkins LN 《The Journal of invasive cardiology》2005,17(6):292-295
The purpose of this article is to describe several inadvertent perforations of external carotid artery branches that occurred in our laboratory during planned carotid artery stenting procedures. When known, the mechanism of the perforation is described. The treatment of these complications is discussed, along with a more general discussion of potential embolic materials. Perforation of branch arteries within the external carotid artery territory during planned carotid revascularization is an uncommon but potentially life-threatening complication. This complication can occur as a result of wire or catheter placement into these vessels. Early recognition of the perforation, prompt treatment of the bleeding, and control of the patient's airway are necessary to avoid a potentially catastrophic outcome. 相似文献