全文获取类型
收费全文 | 406篇 |
免费 | 22篇 |
专业分类
428篇 |
出版年
2022年 | 3篇 |
2021年 | 6篇 |
2019年 | 4篇 |
2018年 | 8篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 8篇 |
2014年 | 13篇 |
2013年 | 9篇 |
2012年 | 20篇 |
2011年 | 13篇 |
2010年 | 8篇 |
2009年 | 6篇 |
2008年 | 13篇 |
2007年 | 27篇 |
2006年 | 34篇 |
2005年 | 23篇 |
2004年 | 22篇 |
2003年 | 24篇 |
2002年 | 22篇 |
2001年 | 6篇 |
2000年 | 12篇 |
1999年 | 18篇 |
1998年 | 8篇 |
1997年 | 10篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 8篇 |
1984年 | 4篇 |
1983年 | 7篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1971年 | 5篇 |
1970年 | 2篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1960年 | 1篇 |
排序方式: 共有428条查询结果,搜索用时 15 毫秒
51.
52.
Nagaki K Yamamura H Shimada S Saito T Hisanaga S Taoka M Isobe T Ichimura T 《Biochemistry》2006,45(21):6733-6740
Although recent studies show that the 14-3-3 protein is a negative regulator of ubiquitin E3 protein ligases, the molecular mechanism remains largely unknown. We previously demonstrated that 14-3-3 specifically binds one of the E3 enzymes, Nedd4-2 (a human gene product of KIAA0439, termed hNedd4-2), which can be phosphorylated by serum glucocorticoid-inducible protein kinase 1 (SGK1); this binding protects the phosphorylated/inactive hNedd4-2 from phosphatase-catalyzed dephosphorylation [Ichimura, T., et al. (2005) J. Biol. Chem. 280, 13187-13194]. Here we report an additional mechanism of 14-3-3-mediated regulation of hNedd4-2. Using surface plasmon resonance spectrometry, we show that 14-3-3 inhibits the interaction between the WW domains of hNedd4-2 and the PY motif of the epithelial Na(+) channel, ENaC. The inhibition was dose-dependent and was dependent on SGK1-catalyzed phosphorylation of Ser468 located between the WW domains. Importantly, a mutant of hNedd4-2, which can be phosphorylated by SGK1 but cannot bind 14-3-3, reduced SGK1-mediated stimulation of the ENaC-induced current in Xenopus laevis oocytes. In addition, 14-3-3 had similar effects on hNedd4-2 that had been phosphorylated by cAMP-dependent protein kinase (PKA). Our results, together with the recent finding on 14-3-3/parkin interactions [Sato, S., et al. (2006) EMBO J. 25, 211-221], suggest that 14-3-3 suppresses ubiquitin E3 ligase activities by inhibiting the formation of the enzyme/substrate complex. 相似文献
53.
Mycobacterium avium-intracellulare complex is a species of acid-fast microorganisms that cause opportunistic infections in immuno-compromised hosts. The cell wall of this microbe is rich in glycopeptidolipids (GPLs), which are composed of a fatty acyl moiety, several sugar moieties and a tripeptide-amino alcohol, D-Phe-D-alloThr-D-Ala-L-Alaninol. GPLs have molecular diversity in the hydrocarbon chain variety of the acyl moiety, and methyl and acetyl modifications of the sugar moiety, but there has been no report of any variety in the tripeptide-amino alcohol component. In this study, we showed two atypical GPL ions of 34 or 48 Da less than the dominant ions of GPLs by mass spectrometry. These ions could not be explained as resulting from conventional molecular diversity. To investigate the reasons why these ions appeared, we made a preparation of the lipopeptide component from intact GPLs and structurally analyzed the molecules. The results suggested that these atypical ions differed from the typical ions in amino acid composition. We further determined its composition by amino acid analysis, and the results showed that the tripeptide portion of the two atypical ions is composed of the Val-alloThr-Ala or the Leu-alloThr-Ala amino acid sequence. In this study, we present novel variations in the tripeptide portion of GPL molecules. 相似文献
54.
Ruts T Matsubara S Wiese-Klinkenberg A Walter A 《Journal of experimental botany》2012,63(9):3339-3351
Plants are sessile organisms forced to adjust to their surrounding environment. In a single plant the photoautotrophic shoot is exposed to pronounced environmental variations recurring in a day-night 24?h (diel) cycle, whereas the heterotrophic root grows in a temporally less fluctuating environment. The contrasting habitats of shoots and roots are reflected in different diel growth patterns and their responsiveness to environmental stimuli. Differences between diel leaf growth patterns of mono- and dicotyledonous plants correspond to their different organization and placement of growth zones. In monocots, heterotrophic growth zones are organized linearly and protected from the environment by sheaths of older leaves. In contrast, photosynthetically active growth zones of dicot leaves are exposed directly to the environment and show characteristic, species-specific diel growth patterns. It is hypothesized that the different exposure to environmental constraints and simultaneously the sink/source status of the growing organs may have induced distinct endogenous control of diel growth patterns in roots and leaves of monocot and dicot plants. Confronted by strong temporal fluctuations in environment, the circadian clock may facilitate robust intrinsic control of leaf growth in dicot plants. 相似文献
55.
Ryoji Shinya Yuko Takeuchi Keita Ichimura Shuhei Takemoto Kazuyoshi Futai 《Applied Entomology and Zoology》2012,47(4):341-350
Pine wilt disease (PWD) caused by the pine wood nematode, Bursaphelenchus xylophilus (Steiner and Buhrer) Nickle, has become a worldwide problem. The pathogenic mechanism of PWD continues to remain controversial, which in part may be attributed to the lack of universal materials of B. xylophilus with a high genetic purity. The intrinsic high genetic diversity in B. xylophilus isolates/populations must be a fatal obstacle for performing forward genetics and other molecular approaches to controlling them. We conducted a series of successive full-sib mating of conventional isolates of B. xylophilus to establish a set of inbred strains. Using DNA markers, we also determined their genetic diversity and biological characteristics, such as virulence and reproductive ability. Consequently, the newly established strains yielded a higher genetic purity than the conventional isolates and showed varying virulence despite sharing a common ancestor. The significance of this study lies not only in establishing a set of inbred strains of B. xylophilus with the certification of their purity but also in demonstrating that avirulent strain(s) with a genotype similar to the virulent strains can be obtained by simple successive full-sib mating. This technique is one of the most powerful tools for elucidating the pathogenic mechanism(s) of PWD. 相似文献
56.
Martin Stegmann Ryan G. Anderson Kazuya Ichimura Tamara Pecenkova Patrick Reuter Viktor ?ársky John M. McDowell Ken Shirasu Marco Trujillo 《The Plant cell》2012,24(11):4703-4716
Plant pathogens are perceived by pattern recognition receptors, which are activated upon binding to pathogen-associated molecular patterns (PAMPs). Ubiquitination and vesicle trafficking have been linked to the regulation of immune signaling. However, little information exists about components of vesicle trafficking involved in immune signaling and the mechanisms that regulate them. In this study, we identified Arabidopsis thaliana Exo70B2, a subunit of the exocyst complex that mediates vesicle tethering during exocytosis, as a target of the plant U-box–type ubiquitin ligase 22 (PUB22), which acts in concert with PUB23 and PUB24 as a negative regulator of PAMP-triggered responses. We show that Exo70B2 is required for both immediate and later responses triggered by all tested PAMPs, suggestive of a role in signaling. Exo70B2 is also necessary for the immune response against different pathogens. Our data demonstrate that PUB22 mediates the ubiquitination and degradation of Exo70B2 via the 26S Proteasome. Furthermore, degradation is regulated by the autocatalytic turnover of PUB22, which is stabilized upon PAMP perception. We therefore propose a mechanism by which PUB22-mediated degradation of Exo70B2 contributes to the attenuation of PAMP-induced signaling. 相似文献
57.
Lutein epoxide cycle, light harvesting and photoprotection in species of the tropical tree genus Inga 总被引:2,自引:0,他引:2
Matsubara S Krause GH Seltmann M Virgo A Kursar TA Jahns P Winter K 《Plant, cell & environment》2008,31(4):548-561
Dynamics and possible function of the lutein epoxide (Lx) cycle, that is, the reversible conversion of Lx to lutein (L) in the light-harvesting antennae, were investigated in leaves of tropical tree species. Photosynthetic pigments were quantified in nine Inga species and species from three other genera. In Inga , Lx levels were high in shade leaves (mostly above 20 mmol mol−1 chlorophyll) and low in sun leaves. In Virola surinamensis , both sun and shade leaves exhibited very high Lx contents (about 60 mmol mol−1 chlorophyll). In Inga marginata grown under high irradiance, Lx slowly accumulated within several days upon transfer to deep shade. When shade leaves of I. marginata were briefly exposed to the sunlight, both violaxanthin and Lx were quickly de-epoxidized. Subsequently, overnight recovery occurred only for violaxanthin, not for Lx. In such leaves, containing reduced levels of Lx and increased levels of L, chlorophyll fluorescence induction showed significantly slower reduction of the photosystem II electron acceptor, Q A , and faster formation as well as a higher level of non-photochemical quenching. The results indicate that slow Lx accumulation in Inga leaves may improve light harvesting under limiting light, while quick de-epoxidation of Lx to L in response to excess light may enhance photoprotection. 相似文献
58.
Ichimura Y Kumanomidou T Sou YS Mizushima T Ezaki J Ueno T Kominami E Yamane T Tanaka K Komatsu M 《The Journal of biological chemistry》2008,283(33):22847-22857
Impairment of autophagic degradation of the ubiquitin- and LC3-binding protein "p62" leads to the formation of cytoplasmic inclusion bodies. However, little is known about the sorting mechanism of p62 to autophagic degradation. Here we identified a motif of murine p62 consisting of 11 amino acids (Ser334-Ser344) containing conserved acidic and hydrophobic residues across species, as an LC3 recognition sequence (LRS). The crystal structure of the LC3-LRS complex at 1.56 angstroms resolution revealed interaction of Trp340 and Leu343 of p62 with different hydrophobic pockets on the ubiquitin fold of LC3. In vivo analyses demonstrated that p62 mutants lacking LC3 binding ability accumulated without entrapping into autophagosomes in the cytoplasm and subsequently formed ubiquitin-positive inclusion bodies as in autophagy-deficient cells. These results demonstrate that the intracellular level of p62 is tightly regulated by autophagy through the direct interaction of LC3 with p62 and reveal that selective turnover of p62 via autophagy controls inclusion body formation. 相似文献
59.
Ohsawa S Watanabe T Katada T Nishina H Miura M 《Biochemical and biophysical research communications》2008,371(4):639-643
Apoptosis is associated with morphological changes, including membrane blebbing, cell shrinkage, and chromatin condensation. However, the molecular mechanisms of the dynamic changes in cellular components during apoptosis are largely unknown. Here we developed a new rat monoclonal antibody, 9B1, that specifically immunolabeled dying cells in tissues and in cell cultures. The 9B1 antibody labeled the cytoplasm of apoptotic cells in a caspase-dependent manner. We identified human brain abundant membrane attached signal protein 1 (hBASP1) as the 9B1 antigen using the liquid chromatography with tandem mass spectrometry (LC/MS/MS) method. hBASP1 was present in the nucleus of HeLa cells, but relocated from the nucleus to the cytoplasm after the caspase activation step of apoptosis. Immunostaining analysis revealed that 9B1 preferentially labeled this cytoplasmic form of hBASP1. Labeling by 9B1 to distinguish apoptotic changes could be a novel criterion for determining whether cells with activated caspases are fated for survival or death. 相似文献
60.
Actin filament organization of foot processes in rat podocytes. 总被引:14,自引:0,他引:14
Koichiro Ichimura Hidetake Kurihara Tatsuo Sakai 《The journal of histochemistry and cytochemistry》2003,51(12):1589-1600
The foot processes of podocytes possess abundant microfilaments and modulate glomerular filtration. We investigated the actin filament organization of foot processes in adult rat podocytes and the formation of the actin cytoskeletal system of immature podocytes during glomerulogenesis. Electron microscopy revealed two populations of actin cytoskeletons in foot processes of adult podocytes. One is the actin bundle running above the level of slit diaphragms and the other is the cortical actin network located beneath the plasmalemma. Immunogold labeling for actin-binding proteins demonstrated that alpha-actinin and synaptopodin were localized in the actin bundle, whereas cortactin was in the cortical actin network. Immunofluorescence labeling for actin-binding proteins in immature podocyte showed that alpha-actinin was localized at the level of the junctional complex, whereas cortactin was distributed beneath the entire plasmalemma. Synaptopodin was first observed along the basal plasmalemma from the advanced S-shaped body to the capillary loop stage. We conclude that foot processes have specialized actin filamentous organization and that its establishment is associated with the expression and redistribution of actin-binding proteins during development. 相似文献