全文获取类型
收费全文 | 648篇 |
免费 | 57篇 |
出版年
2022年 | 14篇 |
2021年 | 16篇 |
2020年 | 14篇 |
2019年 | 14篇 |
2018年 | 11篇 |
2017年 | 18篇 |
2016年 | 12篇 |
2015年 | 26篇 |
2014年 | 38篇 |
2013年 | 44篇 |
2012年 | 62篇 |
2011年 | 48篇 |
2010年 | 34篇 |
2009年 | 31篇 |
2008年 | 34篇 |
2007年 | 49篇 |
2006年 | 34篇 |
2005年 | 36篇 |
2004年 | 27篇 |
2003年 | 25篇 |
2002年 | 15篇 |
2001年 | 9篇 |
2000年 | 12篇 |
1999年 | 7篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1981年 | 4篇 |
1980年 | 5篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1970年 | 1篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有705条查询结果,搜索用时 78 毫秒
41.
Spetea C Keren N Hundal T Doan JM Ohad I Andersson B 《The Journal of biological chemistry》2000,275(10):7205-7211
The light exposure history and/or binding of different herbicides at the Q(B) site may induce heterogeneity of photosystem II acceptor side conformation that affects D1 protein degradation under photoinhibitory conditions. GTP was recently found to stimulate the D1 protein degradation of photoinactivated photosystem II (Spetea, C. , Hundal, T., Lohmann, F., and Andersson, B. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 6547-6552). Here we report that GTP enhances the cleavage of the D1 protein D-E loop following exposure of thylakoid membranes to either high light, low light, or repetitive single turnover flashes but not to trypsin. GTP does not stimulate D1 protein degradation in the presence of herbicides known to affect the accessibility of the cleavage site to proteolysis. However, GTP stimulates degradation that can be induced even in darkness in some photosystem II conformers following binding of the PNO8 herbicide (Nakajima, Y., Yoshida, S., Inoue, Y., Yoneyama, K., and Ono, T. (1995) Biochim. Biophys. Acta 1230, 38-44). Both the PNO8- and the light-induced primary cleavage of the D1 protein occur in the grana membrane domains. The subsequent migration of photosytem II containing the D1 protein fragments to the stroma domains for secondary proteolysis is light-activated. We conclude that the GTP effect is not confined to a specific photoinactivation pathway nor to the conformational state of the photosystem II acceptor side. Consequently, GTP does not interact with the site of D1 protein cleavage but rather enhances the activity of the endogenous proteolytic system. 相似文献
42.
Selective Perturbation of Apical Membrane Traffic by Expression of Influenza M2, an Acid-activated Ion Channel, in Polarized Madin–Darby Canine Kidney Cells
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jennifer R. Henkel Gerard Apodaca Yoram Altschuler Stephen Hardy Ora A. Weisz 《Molecular biology of the cell》1998,9(9):2477-2490
The function of acidification along the endocytic pathway is not well understood, in part because the perturbants used to modify compartmental pH have global effects and in some cases alter cytoplasmic pH. We have used a new approach to study the effect of pH perturbation on postendocytic traffic in polarized Madin–Darby canine kidney (MDCK) cells. Influenza M2 is a small membrane protein that functions as an acid-activated ion channel and can elevate the pH of the trans-Golgi network and endosomes. We used recombinant adenoviruses to express the M2 protein of influenza virus in polarized MDCK cells stably transfected with the polymeric immunoglobulin (Ig) receptor. Using indirect immunofluorescence and immunoelectron microscopy, M2 was found to be concentrated at the apical plasma membrane and in subapical vesicles; intracellular M2 colocalized partly with internalized IgA in apical recycling endosomes as well as with the trans-Golgi network marker TGN-38. Expression of M2 slowed the rate of IgA transcytosis across polarized MDCK monolayers. The delay in transport occurred after IgA reached the apical recycling endosome, consistent with the localization of intracellular M2. Apical recycling of IgA was also slowed in the presence of M2, whereas basolateral recycling of transferrin and degradation of IgA were unaffected. By contrast, ammonium chloride affected both apical IgA and basolateral transferrin release. Together, our data suggest that M2 expression selectively perturbs acidification in compartments involved in apical delivery without disrupting other postendocytic transport steps. 相似文献
43.
Dae Won Kim Sung Ho Lee Min Jea Shin Kibom Kim Sae Kwang Ku Jong Kyu Youn Su Bin Cho Jung Hwan Park Chi Hern Lee Ora Son Eun Jeong Sohn Sung-Woo Cho Jong Hoon Park Hyun Ah Kim Kyu Hyung Han Jinseu Park Won Sik Eum Soo Young Choi 《BMB reports》2015,48(11):618-623
FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In the cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI. [BMB Reports 2015; 48(11): 618-623] 相似文献
44.
Detelina Grozeva Keren Carss Olivera Spasic-Boskovic Michael?J. Parker Hayley Archer Helen?V. Firth Soo-Mi Park Natalie Canham Susan?E. Holder Meredith Wilson Anna Hackett Michael Field James?A.B. Floyd UKK Consortium Matthew Hurles F.?Lucy Raymond 《American journal of human genetics》2014,94(4):618-624
To identify further Mendelian causes of intellectual disability (ID), we screened a cohort of 996 individuals with ID for variants in 565 known or candidate genes by using a targeted next-generation sequencing approach. Seven loss-of-function (LoF) mutations—four nonsense (c.1195A>T [p.Lys399∗], c.1333C>T [p.Arg445∗], c.1866C>G [p.Tyr622∗], and c.3001C>T [p.Arg1001∗]) and three frameshift (c.2177_2178del [p.Thr726Asnfs∗39], c.3771dup [p.Ser1258Glufs∗65], and c.3856del [p.Ser1286Leufs∗84])—were identified in SETD5, a gene predicted to encode a methyltransferase. All mutations were compatible with de novo dominant inheritance. The affected individuals had moderate to severe ID with additional variable features of brachycephaly; a prominent high forehead with synophrys or striking full and broad eyebrows; a long, thin, and tubular nose; long, narrow upslanting palpebral fissures; and large, fleshy low-set ears. Skeletal anomalies, including significant leg-length discrepancy, were a frequent finding in two individuals. Congenital heart defects, inguinal hernia, or hypospadias were also reported. Behavioral problems, including obsessive-compulsive disorder, hand flapping with ritualized behavior, and autism, were prominent features. SETD5 lies within the critical interval for 3p25 microdeletion syndrome. The individuals with SETD5 mutations showed phenotypic similarity to those previously reported with a deletion in 3p25, and thus loss of SETD5 might be sufficient to account for many of the clinical features observed in this condition. Our findings add to the growing evidence that mutations in genes encoding methyltransferases regulating histone modification are important causes of ID. This analysis provides sufficient evidence that rare de novo LoF mutations in SETD5 are a relatively frequent (0.7%) cause of ID. 相似文献
45.
46.
47.
Kroata Hazler Pilepić Miranda Morović Filip Orač Marija Šantor Vanja Vejnović 《Biologia》2010,65(5):805-812
The chloroplast DNA of 43 species including 16 sections from the genus Hypericum was studied by PCR-RFLP analysis. The PCR-amplified products of four cpDNA regions, trnC-trnD, psbC-trnS, trnL-trnF and rbcL were digested with four restriction endonucleases. A high level of interspecific variation was detected while intraspecific
diversity was not observed. The resulting parsimony analysis indicated the monophyletic assemblage of the sections Androsaemum, Olympia, Drosocarpium and Trigynobrathys. Monophyly of Hypericum is weakly supported, but close relationships of H. perforatum and H. maculatum are indicated. The members of Ascyreia are weakly resolved, but clustering of H. kouytchense and H. oblongifolium is well supported, however, H. reptans is nested with Olympia. CpDNA profiles and the positions on the parsimony tree indicate that the chloroplast donor among the putative parents of
the hybrid species H. ×inodorum is H. androsaemum. 相似文献
48.
49.
50.
Wiskott-Aldrich syndrome protein (WASP) and WAVE stimulate actin-related protein (Arp)2/3-mediated actin polymerization, leading to diverse downstream effects, including the formation and remodeling of cell surface protrusions, modulation of cell migration, and intracytoplasmic propulsion of organelles and pathogens. Selective inhibitors of individual Arp2/3 activators would enable more exact dissection of WASP- and WAVE-dependent cellular pathways and are potential therapeutic targets for viral pathogenesis. Wiskostatin is a recently described chemical inhibitor that selectively inhibits neuronal WASP (N-WASP)-mediated actin polymerization in vitro. A growing number of recent studies have utilized this drug in vivo to uncover novel cellular functions for N-WASP; however, the selectivity of wiskostatin in intact cells has not been carefully explored. In our studies with this drug, we observed rapid and dose-dependent inhibition of N-WASP-dependent membrane trafficking steps. Additionally, however, we found that addition of wiskostatin inhibited numerous other cellular functions that are not believed to be N-WASP dependent. Further studies revealed that wiskostatin treatment caused a rapid, profound, and irreversible decrease in cellular ATP levels, consistent with its global effects on cell function. Our data caution against the use of this drug as a selective perturbant of N-WASP-dependent actin dynamics in vivo. phosphatidylinositol 4,5-bisphosphate; cytoskeleton; membrane traffic; Arp2/3; actin comets 相似文献