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31.
Yamachika E Tsujigiwa H Matsubara M Hirata Y Kita K Takabatake K Mizukawa N Kaneda Y Nagatsuka H Iida S 《Journal of molecular histology》2012,43(2):223-233
Some progress has been made in development of methods to regenerate bone from cultured cells, however no method is put to
practical use. Here, we developed methods to isolate, purify, and expand mesenchymal stem cells (MSCs) from mouse compact
bone that may be used to regenerate bone in vivo. These cells were maintained in long-term culture and were capable of differentiating
along multiple lineages, including chondrocyte, osteocyte, and adipocyte trajectories. We used standard cell isolation and
culture methods to establish cell cultures from mouse compact bone and bone marrow. Cultures were grown in four distinct media
to determine the optimal composition of culture medium for bone-derived MSCs. Putative MSCs were subjected to flow cytometry,
alkaline phosphatase assays, immunohistochemical staining, and several differentiation assays to assess cell identity, protein
expression, and developmental potential. Finally, we used an in vivo bone formation assay to determine whether putative MSCs
were capable of regenerating bone. We found that compact bone of mice was a better source of MCSs than the bone marrow, that
growth in plastic flasks served to purify MSCs from hematopoietic cells, and that MSCs grown in basic fibroblast growth factor
(bFGF)-conditioned medium were, based on multiple criteria, superior to those grown in leukemia inhibitory factor-conditioned
medium. Moreover, we found that the MSCs isolated from compact bone and grown in bFGF-conditioned medium were capable of supporting
bone formation in vivo. The methods and results described here have implications for understanding MSC biology and for clinical
purpose. 相似文献
32.
Small GTPase protein Rac-1 is activated with maturation and regulates cell morphology and function in chondrocytes 总被引:1,自引:0,他引:1
Kerr BA Otani T Koyama E Freeman TA Enomoto-Iwamoto M 《Experimental cell research》2008,314(6):1301-1312
During maturation, chondrocytes undergo changes in morphology, matrix production, and gene expression; however, it remains unclear whether these are interrelated. In this study, we examined whether Rho GTPases were involved in these regulatory interplays. Levels of active Rho GTPases were assayed in immature and mature primary chondrocytes. We found that activation of Rac-1 and Cdc42 increased with maturation, whereas RhoA levels remained unchanged. GFP-tagged Rho GTPases tracked cellular localization. Rac-1 was enriched at the cell membrane where it co-localized with cortical actin, while RhoA and Cdc42 were cytoplasmic. To test the roles of Rac-1 in chondrocyte maturation, we force-expressed constitutively active or dominant negative forms of Rac-1 and assessed phenotypic consequences in primary chondrocytes. Activated Rac-1 expression induced chondrocyte enlargement and increased matrix metalloproteinase expression, which are characteristic of mature chondrocytes. Conversely, Rac-1 inactivation diminished adhesion, decreased alkaline phosphatase activity, and stimulated functions typical of immature chondrocytes. Exposure to a pro-maturation factor, Wnt3A, induced a flattened and enlarged morphology accompanied by peripheral Rac-1 re-arrangement. Wnt3A stimulated Tiam1 expression and Rac-1 activation, while DN-Rac-1 inhibited Wnt3A-induced cell spreading. Our data provide strong evidence that Rac-1 coordinates changes in chondrocyte phenotype and function and stimulates the maturation process essential for skeletal development. 相似文献
33.
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
34.
The Ca(2+) channel alpha(1B) subunit is a pore-forming component capable of generating N-type Ca(2+) channel activity. Although the N-type Ca(2+) channel plays a role in a variety of neuronal functions, alpha(1B)-deficient mice with a CBA/JN genetic background show no apparent behavioral or anatomical-histological abnormality, presumably owing to compensation by other Ca(2+) channels. In this study, we examined the mRNA expression of the alpha(1A), alpha(1C), alpha(1D), alpha(1E), beta(1), beta(2), beta(3) and beta(4) subunits in the olfactory bulb, cerebral cortex, hippocampus and cerebellum of alpha(1B)-deficient mice. We found that the mRNA expression levels of the alpha(1A), alpha(1C), alpha(1D), alpha(1E), beta(1), beta(2), beta(3) and beta(4) subunits were the same in the olfactory bulbs of wild, heterozygous and homozygous alpha(1B)-deficient mice. In the cerebral cortex, alpha(1A) mRNA in homozygous alpha(1B)-deficient mice was expressed at a higher level than in wild or heterozygous mice, but no difference in the expression levels of the alpha(1C), alpha(1D), alpha(1E), beta(1), beta(2), beta(3) and beta(4) subunits was found among wild, heterozygous and homozygous mice. In hippocampus and cerebellum, beta(4) mRNA in homozygous alpha(1B)-deficient mice was expressed at a higher level than in wild or heterozygous mice, but no difference in the expression levels of the alpha(1A), alpha(1C), alpha(1D), alpha(1E), beta(1), beta(2) and beta(3) subunits was found among wild, heterozygous and homozygous mice. These results suggest that the compensatory mechanisms differ in different brain regions of alpha(1B)-deficient mice with a CBA/JN genetic background. 相似文献
35.
Matsumoto N Ezaki J Komatsu M Takahashi K Mineki R Taka H Kikkawa M Fujimura T Takeda-Ezaki M Ueno T Tanaka K Kominami E 《Biochemical and biophysical research communications》2008,368(3):643-649
Autophagy is a bulk protein degradation system for the entire organelles and cytoplasmic proteins. Previously, we have shown the liver dysfunction by autophagy deficiency. To examine the pathological effect of autophagy deficiency, we examined protein composition and their levels in autophagy-deficient liver by the proteomic analysis. While impaired autophagy led to an increase in total protein mass, the protein composition was largely unchanged, consistent with non-selective proteins/organelles degradation of autophagy. However, a series of oxidative stress-inducible proteins, including glutathione S-transferase families, protein disulfide isomerase and glucose-regulated proteins were specifically increased in autophagy-deficient liver, probably due to enhanced gene expression, which is induced by accumulation of Nrf2 in the nuclei of mutant hepatocytes. Our results suggest that autophagy deficiency causes oxidative stress, and such stress might be the main cause of liver injury in autophagy-deficient liver. 相似文献
36.
Distinct roles for U‐type proteins in iron–sulfur cluster biosynthesis revealed by genetic analysis of the Bacillus subtilis sufCDSUB operon 下载免费PDF全文
Nao Yokoyama Chihiro Nonaka Yukari Ohashi Masaharu Shioda Takuya Terahata Wen Chen Kotomi Sakamoto Chihiro Maruyama Takuya Saito Eiki Yuda Naoyuki Tanaka Takashi Fujishiro Tomohisa Kuzuyama Kei Asai Yasuhiro Takahashi 《Molecular microbiology》2018,107(6):688-703
The biosynthesis of iron–sulfur (Fe–S) clusters in Bacillus subtilis is mediated by the SUF‐like system composed of the sufCDSUB gene products. This system is unique in that it is a chimeric machinery comprising homologues of E. coli SUF components (SufS, SufB, SufC and SufD) and an ISC component (IscU). B. subtilis SufS cysteine desulfurase transfers persulfide sulfur to SufU (the IscU homologue); however, it has remained controversial whether SufU serves as a scaffold for Fe–S cluster assembly, like IscU, or acts as a sulfur shuttle protein, like E. coli SufE. Here we report that reengineering of the isoprenoid biosynthetic pathway in B. subtilis can offset the indispensability of the sufCDSUB operon, allowing the resultant Δsuf mutants to grow without detectable Fe–S proteins. Heterologous bidirectional complementation studies using B. subtilis and E. coli mutants showed that B. subtilis SufSU is interchangeable with E. coli SufSE but not with IscSU. In addition, functional similarity in SufB, SufC and SufD was observed between B. subtilis and E. coli. Our findings thus indicate that B. subtilis SufU is the protein that transfers sulfur from SufS to SufB, and that the SufBCD complex is the site of Fe–S cluster assembly. 相似文献
37.
38.
Shinji Kikuchi Raju Bheemanahalli Krishna S.V. Jagadish Etsushi Kumagai Yusuke Masuya Eiki Kuroda Chitra Raghavan Michael Dingkuhn Akira Abe Hiroyuki Shimono 《Plant, cell & environment》2017,40(8):1565-1575
Phenotypic plasticity of plants in response to environmental changes is important for adapting to changing climate. Less attention has been paid to exploring the advantages of phenotypic plasticity in resource‐rich environments to enhance the productivity of agricultural crops. Here, we examined genetic variation for phenotypic plasticity in indica rice (Oryza sativa L.) across two diverse panels: (1) a Phenomics of Rice Adaptation and Yield (PRAY) population comprising 301 accessions; and (2) a Multi‐parent Advanced Generation Inter‐Cross (MAGIC) indica population comprising 151 accessions. Altered planting density was used as a proxy for elevated atmospheric CO2 response. Low planting density significantly increased panicle weight per plant compared with normal density, and the magnitude of the increase ranged from 1.10 to 2.78 times among accessions for the PRAY population and from 1.05 to 2.45 times for the MAGIC population. Genome‐wide‐association studies validate three E nvironmental R esponsiveness (ER) candidate alleles (qER1–3) that were associated with relative response of panicle weight to low density. Two of these alleles were tested in 13 genotypes to clarify their biomass responses during vegetative growth under elevated CO2 in Japan. Our study provides evidence for polymorphisms that control rice phenotypic plasticity in environments that are rich in resources such as light and CO2. 相似文献
39.
Complex structure of cytochrome c–cytochrome c oxidase reveals a novel protein–protein interaction mode 下载免费PDF全文
Satoru Shimada Kyoko Shinzawa‐Itoh Junpei Baba Shimpei Aoe Atsuhiro Shimada Eiki Yamashita Jiyoung Kang Masaru Tateno Shinya Yoshikawa Tomitake Tsukihara 《The EMBO journal》2017,36(3):291-300
Mitochondrial cytochrome c oxidase (CcO) transfers electrons from cytochrome c (Cyt.c) to O2 to generate H2O, a process coupled to proton pumping. To elucidate the mechanism of electron transfer, we determined the structure of the mammalian Cyt.c–CcO complex at 2.0‐Å resolution and identified an electron transfer pathway from Cyt.c to CcO. The specific interaction between Cyt.c and CcO is stabilized by a few electrostatic interactions between side chains within a small contact surface area. Between the two proteins are three water layers with a long inter‐molecular span, one of which lies between the other two layers without significant direct interaction with either protein. Cyt.c undergoes large structural fluctuations, using the interacting regions with CcO as a fulcrum. These features of the protein–protein interaction at the docking interface represent the first known example of a new class of protein–protein interaction, which we term “soft and specific”. This interaction is likely to contribute to the rapid association/dissociation of the Cyt.c–CcO complex, which facilitates the sequential supply of four electrons for the O2 reduction reaction. 相似文献
40.
Ebato C Uchida T Arakawa M Komatsu M Ueno T Komiya K Azuma K Hirose T Tanaka K Kominami E Kawamori R Fujitani Y Watada H 《Cell metabolism》2008,8(4):325-332
Autophagy is an evolutionarily conserved machinery for bulk degradation of cytoplasmic components. Here, we report upregulation of autophagosome formation in pancreatic beta cells in diabetic db/db and in nondiabetic high-fat-fed C57BL/6 mice. Free fatty acids (FFAs), which can cause peripheral insulin resistance associated with diabetes, induced autophagy in beta cells. Genetic ablation of atg7 in beta cells resulted in degeneration of islets and impaired glucose tolerance with reduced insulin secretion. While high-fat diet stimulated beta cell autophagy in control mice, it induced profound deterioration of glucose tolerance in autophagy-deficient mutants, partly because of the lack of compensatory increase in beta cell mass. These findings suggest that basal autophagy is important for maintenance of normal islet architecture and function. The results also identified a unique role for inductive autophagy as an adaptive response of beta cells in the presence of insulin resistance induced by high-fat diet. 相似文献