全文获取类型
收费全文 | 285篇 |
免费 | 32篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 3篇 |
2020年 | 4篇 |
2019年 | 2篇 |
2018年 | 5篇 |
2017年 | 10篇 |
2016年 | 11篇 |
2015年 | 14篇 |
2014年 | 20篇 |
2013年 | 17篇 |
2012年 | 34篇 |
2011年 | 31篇 |
2010年 | 7篇 |
2009年 | 10篇 |
2008年 | 16篇 |
2007年 | 22篇 |
2006年 | 12篇 |
2005年 | 12篇 |
2004年 | 9篇 |
2003年 | 13篇 |
2002年 | 6篇 |
2001年 | 2篇 |
2000年 | 6篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 5篇 |
1981年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 2篇 |
排序方式: 共有317条查询结果,搜索用时 453 毫秒
21.
Xu J Zheng SL Chang B Smith JR Carpten JD Stine OC Isaacs SD Wiley KE Henning L Ewing C Bujnovszky P Bleeker ER Walsh PC Trent JM Meyers DA Isaacs WB 《Human genetics》2001,108(4):335-345
Three prostate cancer susceptibility genes have been reported to be linked to different regions on chromosome 1: HPC1 at 1q24-25, PCAP at 1q42-43, and CAPB at 1p36. Replication studies analyzing each of these regions have yielded inconsistent results. To evaluate linkage across this chromosome systematically, we performed multipoint linkage analyses with 50 microsatellite markers spanning chromosome 1 in 159 hereditary prostate cancer families (HPC), including 79 families analyzed in the original report describing HPC1 linkage. The highest lod scores for the complete dataset of 159 families were observed at 1q24-25 at which the parametric lod score assuming heterogeneity (hlod) was 2.54 (P=0.0006) with an allele sharing lod of 2.34 (P=0.001) at marker D1S413, although only weak evidence was observed in the 80 families not previously analyzed for this region (hlod=0.44, P=0.14, and allele sharing lod=0.67, P=0.08). In the complete data set, the evidence for linkage across this region was very broad, with allele sharing lod scores greater than 0.5 extending approximately 100 cM from 1p13 to 1q32, possibly indicating the presence of multiple susceptibility genes. Elsewhere on chromosome 1, some evidence of linkage was observed at 1q42-43, with a peak allele sharing lod of 0.56 (P=0.11) and hlod of 0.24 (P=0.25) at D1S235. For analysis of the CAPB locus at 1p36, we focused on six HPC families in our collection with a history of primary brain cancer; four of these families had positive linkage results at 1p36, with a peak allele sharing lod of 0.61 (P=0.09) and hlod of 0.39 (P=0.16) at D1S407 in all six families. These results are consistent with the heterogeneous nature of hereditary prostate cancer, and the existence of multiple loci on chromosome 1 for this disease. 相似文献
22.
Activation Control of pur Gene Expression in Lactococcus lactis: Proposal for a Consensus Activator Binding Sequence Based on Deletion Analysis and Site-Directed Mutagenesis of purC and purD Promoter Regions 总被引:1,自引:0,他引:1 下载免费PDF全文
23.
24.
Magnus Kjaergaard Ann‒Beth Nørholm Ruth Hendus‒Altenburger Stine F. Pedersen Flemming M. Poulsen Birthe B. Kragelund 《Protein science : a publication of the Protein Society》2010,19(8):1555-1564
Structural characterization of intrinsically disordered proteins (IDPs) is mandatory for deciphering their potential unique physical and biological properties. A large number of circular dichroism (CD) studies have demonstrated that a structural change takes place in IDPs with increasing temperature, which most likely reflects formation of transient α-helices or loss of polyproline II (PPII) content. Using three IDPs, ACTR, NHE1, and Spd1, we show that the temperature-induced structural change is common among IDPs and is accompanied by a contraction of the conformational ensemble. This phenomenon was explored at residue resolution by multidimensional NMR spectroscopy. Intrinsic chemical shift referencing allowed us to identify regions of transiently formed helices and their temperature-dependent changes in helicity. All helical regions were found to lose rather than gain helical structures with increasing temperature, and accordingly these were not responsible for the change in the CD spectra. In contrast, the nonhelical regions exhibited a general temperature-dependent structural change that was independent of long-range interactions. The temperature-dependent CD spectroscopic signature of IDPs that has been amply documented can be rationalized to represent redistribution of the statistical coil involving a general loss of PPII conformations. 相似文献
25.
Anne Sofie Busk Heitmann Ali Asghar Hakami Zanjani Martin Berg Klenow Anna Mularski Stine Lauritzen Snder Frederik Wendelboe Lund Theresa Louise Boye Catarina Dias Poul Martin Bendix Adam Cohen Simonsen Himanshu Khandelia Jesper Nylandsted 《The Journal of biological chemistry》2021,297(2)
Repair of damaged plasma membrane in eukaryotic cells is largely dependent on the binding of annexin repair proteins to phospholipids. Changing the biophysical properties of the plasma membrane may provide means to compromise annexin-mediated repair and sensitize cells to injury. Since, cancer cells experience heightened membrane stress and are more dependent on efficient plasma membrane repair, inhibiting repair may provide approaches to sensitize cancer cells to plasma membrane damage and cell death. Here, we show that derivatives of phenothiazines, which have widespread use in the fields of psychiatry and allergy treatment, strongly sensitize cancer cells to mechanical-, chemical-, and heat-induced injury by inhibiting annexin-mediated plasma membrane repair. Using a combination of cell biology, biophysics, and computer simulations, we show that trifluoperazine acts by thinning the membrane bilayer, making it more fragile and prone to ruptures. Secondly, it decreases annexin binding by compromising the lateral diffusion of phosphatidylserine, inhibiting the ability of annexins to curve and shape membranes, which is essential for their function in plasma membrane repair. Our results reveal a novel avenue to target cancer cells by compromising plasma membrane repair in combination with noninvasive approaches that induce membrane injuries. 相似文献
26.
27.
Klausen TK Bergdahl A Hougaard C Christophersen P Pedersen SF Hoffmann EK 《Journal of cellular physiology》2007,210(3):831-842
Recent evidence implicates the volume-regulated anion current (VRAC) and other anion currents in control or modulation of cell cycle progression; however, the precise involvement of anion channels in this process is unclear. Here, Cl- currents in Ehrlich Lettre Ascites (ELA) cells were monitored during cell cycle progression, under three conditions: (i) after osmotic swelling (i.e., VRAC), (ii) after an increase in the free intracellular Ca2+ concentration (i.e., the Ca2+-activated Cl- current, CaCC), and (iii) under steady-state isotonic conditions. The maximal swelling-activated VRAC current decreased in G1 and increased in early S phase, compared to that in G0. The isotonic steady-state current, which seems to be predominantly VRAC, also decreased in G1, and increased again in early S phase, to a level similar to that in G0. In contrast, the maximal CaCC current (500 nM free Ca2+ in the pipette), was unaltered from G0 to G1, but decreased in early S phase. A novel high-affinity anion channel inhibitor, the acidic di-aryl-urea NS3728, which inhibited both VRAC and CaCC, attenuated ELA cell growth, suggesting a possible mechanistic link between cell cycle progression and cell cycle-dependent changes in the capacity for conductive Cl- transport. It is suggested that in ELA cells, entrance into the S phase requires an increase in VRAC activity and/or an increased potential for regulatory volume decrease (RVD), and at the same time a decrease in CaCC magnitude. 相似文献
28.
29.
Protein phosphorylation/dephosphorylation and cytoskeletal reorganization regulate the Na+-K+-2Cl cotransporter (NKCC1) during osmotic shrinkage; however, the mechanisms involved are unclear. We show that in cytoplasts, plasma membrane vesicles detached from Ehrlich ascites tumor cells (EATC) by cytochalasin treatment, NKCC1 activity evaluated as bumetanide-sensitive 86Rb influx was increased compared with the basal level in intact cells yet could not be further increased by osmotic shrinkage. Accordingly, cytoplasts exhibited no regulatory volume increase after shrinkage. In cytoplasts, cortical F-actin organization was disrupted, and myosin II, which in shrunken EATC translocates to the cortical region, was absent. Moreover, NKCC1 activity was essentially insensitive to the myosin light chain kinase (MLCK) inhibitor ML-7, a potent blocker of shrinkage-induced NKCC1 activity in intact EATC. Cytoplast NKCC1 activity was potentiated by the Ser/Thr protein phosphatase inhibitor calyculin A, partially inhibited by the protein kinase A inhibitor H89, and blocked by the broad protein kinase inhibitor staurosporine. Cytoplasts exhibited increased protein levels of NKCC1, Ste20-related proline- and alanine-rich kinase (SPAK), and oxidative stress response kinase 1, yet they lacked the shrinkage-induced plasma membrane translocation of SPAK observed in intact cells. The basal phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was increased in cytoplasts compared with intact cells, yet in contrast to the substantial activation in shrunken intact cells, p38 MAPK could not be further activated by shrinkage of the cytoplasts. Together these findings indicate that shrinkage activation of NKCC1 in EATC is dependent on the cortical F-actin network, myosin II, and MLCK. F-actin; Na+-K+-2Cl cotransporter; myosin light chain kinase; protein kinase A 相似文献
30.
John W Cole Adam C Naj Jeffrey R O'Connell Oscar C Stine John D Sorkin Marcella A Wozniak Barney J Stern Manuel Yepes Daniel A Lawrence Laurie J Reinhart Dudley K Strickland Braxton D Mitchell Steven J Kittner 《BMC neurology》2007,7(1):1-7