全文获取类型
收费全文 | 179篇 |
免费 | 0篇 |
国内免费 | 1篇 |
学科分类
自然科学 | 180篇 |
出版年
2022年 | 1篇 |
2020年 | 1篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 1篇 |
2014年 | 4篇 |
2012年 | 4篇 |
2011年 | 8篇 |
2010年 | 2篇 |
2009年 | 5篇 |
2008年 | 9篇 |
2007年 | 9篇 |
2006年 | 5篇 |
2005年 | 6篇 |
2004年 | 8篇 |
2003年 | 4篇 |
2002年 | 7篇 |
2001年 | 8篇 |
2000年 | 10篇 |
1999年 | 5篇 |
1994年 | 1篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1973年 | 2篇 |
1972年 | 4篇 |
1971年 | 5篇 |
1970年 | 8篇 |
1969年 | 8篇 |
1968年 | 2篇 |
1967年 | 6篇 |
1966年 | 3篇 |
1963年 | 1篇 |
1962年 | 1篇 |
1961年 | 2篇 |
1957年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有180条查询结果,搜索用时 0 毫秒
1.
2.
Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome 总被引:7,自引:0,他引:7
Arts HH Doherty D van Beersum SE Parisi MA Letteboer SJ Gorden NT Peters TA Märker T Voesenek K Kartono A Ozyurek H Farin FM Kroes HY Wolfrum U Brunner HG Cremers FP Glass IA Knoers NV Roepman R 《Nature genetics》2007,39(7):882-888
Protein-protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis (NPHP), Leber congenital amaurosis, Senior-L?ken syndrome (SLSN) or Joubert syndrome (JBTS). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1 (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt this interaction. RPGRIP1L is ubiquitously expressed, and its protein product localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene for JBTS and identified loss-of-function mutations in three families with typical JBTS, including the characteristic mid-hindbrain malformation. This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder. 相似文献
3.
Gout AM;ADPKD Gene Variant Consortium Ravine D Harris PC Rossetti S Peters D Breuning M Henske EP Koizumi A Inoue S Shimizu Y Thongnoppakhun W Yenchitsomanus PT Deltas C Sandford R Torra R Turco AE Jeffery S Fontes M Somlo S Furu LM Smulders YM Mercier B Ferec C Burtey S Pei Y Kalaydjieva L Bogdanova N McCluskey M Geon LJ Wouters CH Reiterova J Stekrová J San Millan JL Aguiari G Del Senno L 《Nature genetics》2007,39(4):427-428
4.
Barker N van Es JH Kuipers J Kujala P van den Born M Cozijnsen M Haegebarth A Korving J Begthel H Peters PJ Clevers H 《Nature》2007,449(7165):1003-1007
The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. It is currently believed that four to six crypt stem cells reside at the +4 position immediately above the Paneth cells in the small intestine; colon stem cells remain undefined. Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49) was selected from a panel of intestinal Wnt target genes for its restricted crypt expression. Here, using two knock-in alleles, we reveal exclusive expression of Lgr5 in cycling columnar cells at the crypt base. In addition, Lgr5 was expressed in rare cells in several other tissues. Using an inducible Cre knock-in allele and the Rosa26-lacZ reporter strain, lineage-tracing experiments were performed in adult mice. The Lgr5-positive crypt base columnar cell generated all epithelial lineages over a 60-day period, suggesting that it represents the stem cell of the small intestine and colon. The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers. 相似文献
5.
Oxysterols direct immune cell migration via EBI2 总被引:1,自引:0,他引:1
Hannedouche S Zhang J Yi T Shen W Nguyen D Pereira JP Guerini D Baumgarten BU Roggo S Wen B Knochenmuss R Noël S Gessier F Kelly LM Vanek M Laurent S Preuss I Miault C Christen I Karuna R Li W Koo DI Suply T Schmedt C Peters EC Falchetto R Katopodis A Spanka C Roy MO Detheux M Chen YA Schultz PG Cho CY Seuwen K Cyster JG Sailer AW 《Nature》2011,475(7357):524-527
Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases. The natural ligand for EBI2 has been unknown. Here we describe the identification of 7α,25-dihydroxycholesterol (also called 7α,25-OHC or 5-cholesten-3β,7α,25-triol) as a potent and selective agonist of EBI2. Functional activation of human EBI2 by 7α,25-OHC and closely related oxysterols was verified by monitoring second messenger readouts and saturable, high-affinity radioligand binding. Furthermore, we find that 7α,25-OHC and closely related oxysterols act as chemoattractants for immune cells expressing EBI2 by directing cell migration in vitro and in vivo. A critical enzyme required for the generation of 7α,25-OHC is cholesterol 25-hydroxylase (CH25H). Similar to EBI2 receptor knockout mice, mice deficient in CH25H fail to position activated B cells within the spleen to the outer follicle and mount a reduced plasma cell response after an immune challenge. This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2-oxysterol signalling pathway has an important role in the adaptive immune response. 相似文献
6.
7.
8.
Wesch D Peters C Oberg HH Pietschmann K Kabelitz D 《Cellular and molecular life sciences : CMLS》2011,68(14):2357-2370
Toll-like receptors (TLR) are pattern-recognition receptors that recognize a broad variety of structurally conserved molecules
derived from microbes. The recognition of TLR ligands functions as a primary sensor of the innate immune system, leading to
subsequent indirect activation of the adaptive immunity as well as none-immune cells. However, TLR are also expressed by several
T cell subsets, and the respective ligands can directly modulate their effector functions. The present review summarizes the
recent findings of γδ T cell modulation by TLR ligands. TLR1/2/6, 3, and 5 ligands can act directly in combination with T
cell receptor (TCR) stimulation to enhance cytokine/chemokine production of freshly isolated human γδ T cells. In contrast
to human γδ T cells, murine and bovine γδ T cells can directly respond to TLR2 ligands with increased proliferation and cytokine
production in a TCR-independent manner. Indirect stimulatory effects on IFN-γ production of human and murine γδ T cells via
TLR-ligand activated dendritic cells have been described for TLR2, 3, 4, 7, and 9 ligands. In addition, TLR3 and 7 ligands
indirectly increase tumor cell lysis by human γδ T cells, whereas ligation of TLR8 abolishes the suppressive activity of human
tumor-infiltrating Vδ1 γδ T cells on αβ T cells and dendritic cells. Taken together, these data suggest that TLR-mediated
signals received by γδ T cells enhance the initiation of adaptive immune responses during bacterial and viral infection directly
or indirectly. Moreover, TLR ligands enhance cytotoxic tumor responses of γδ T cells and regulate the suppressive capacity
of γδ T cells. 相似文献
9.
Résumé Chez le rat hypertendu par constriction partielle d'une artère rénale et néphrectomie controlatérale, la suppression chirurgicale de la constriction entraîne une normalisation de la pression artérielle et une excrétion urinaire importante d'eau et de sodium; la ligature préalable de l'uretère empêche la normalisation de la pression. 相似文献
10.
Zusammenfassung Verhaltensversuche, bei denen die Reaktionen des Zwergwelses (Ictalurus nebulosus LeS.) auf künstlich wiedergegebene pseudo-bioelektrische und-hydroelektrische Felder registriert wurden, ergaben, dassIctalurus beim Beutefang die von der Beute hervorgebrachten elektrischen Felder benützen kann und dass in hydroelektrischen Feldern spontan Orientierungsverhalten auftritt. 相似文献