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排序方式: 共有532条查询结果,搜索用时 15 毫秒
41.
Hiroki Shimizu Shinji Tanaka Tadashi Toki Isao Yasumatsu Toshihiko Akimoto Kaoru Morishita Tomonori Yamasaki Takanori Yasukochi Shin Iimura 《Bioorganic & medicinal chemistry letters》2010,20(17):5113-5118
Imidazo[1,2-b]pyridazine derivatives from high-throughput screening were developed as IKKβ inhibitors. By the optimization of the 3- and 6-position of imidazo[1,2-b]pyridazine scaffold, cell-free IKKβ inhibitory activity and TNFα inhibitory activity in THP-1 cell increased. Also, these compounds showed high kinase selectivity. The structure–activity relationship was revealed and the interaction model of imidazo[1,2-b]pyridazine compounds with IKKβ was constructed. 相似文献
42.
Kurisaki I Fukuzawa K Komeiji Y Mochizuki Y Nakano T Imada J Chmielewski A Rothstein SM Watanabe H Tanaka S 《Biophysical chemistry》2007,130(1-2):1-9
A visualization method for inter-fragment interaction energies (IFIEs) of biopolymers is presented on the basis of the fragment molecular orbital (FMO) method. The IFIEs appropriately illustrate the information about the interaction energies between the fragments consisting of amino acids, nucleotides and other molecules. The IFIEs are usually analyzed in a matrix form called an IFIE matrix. Analyzing the IFIE matrix, we detect important fragments for the function of biomolecular systems and quantify the strength of interaction energies based on quantum chemistry, including the effects of charge transfer, electronic polarization and dispersion force. In this study, by analyzing a protein-DNA complex, we report a visual representation of the IFIE matrix, a so-called IFIE map. We comprehensively examine what information the IFIE map contains concerning structures and stabilities of the protein-DNA complex. 相似文献
43.
Comparison of rat mesenchymal stem cells derived from bone marrow,synovium, periosteum,adipose tissue,and muscle 总被引:18,自引:0,他引:18
Yoshimura H Muneta T Nimura A Yokoyama A Koga H Sekiya I 《Cell and tissue research》2007,327(3):449-462
Mesenchymal stem cells (MSCs) are increasingly being reported as occurring in a variety of tissues. Although MSCs from human
bone marrow are relatively easy to harvest, the isolation of rodent MSCs is more difficult, thereby limiting the number of
experiments in vivo. To determine a suitable cell source, we isolated rat MSCs from bone marrow, synovium, periosteum, adipose,
and muscle and compared their properties for yield, expansion, and multipotentiality. After two passages, the cells in each
population were CD11b (−), CD45 (−), and CD90 (+). The colony number per nucleated cells derived from synovium was 100-fold
higher than that for cells derived from bone marrow. With regard to expansion potential, synovium-derived cells were the highest
in colony-forming efficiency, fold increase, and growth kinetics. An in vitro chondrogenesis assay demonstrated that the pellets
derived from synovium were heavier, because of their greater production of cartilage matrix, than those from other tissues,
indicating their superiority in chondrogenesis. Synovium-derived cells retained their chondrogenic potential after a few passages.
The Oil Red-O positive colony-rate assay demonstrated higher adipogenic potential in synovium- and adipose-derived cells.
Alkaline phosphatase activity was greater in periosteum- and muscle-derived cells during calcification. The yield and proliferation
potential of rat MSCs from solid tissues was much better than those from bone marrow. In particular, synovium-derived cells
had the greatest potential for both proliferation and chondrogenesis, indicating their usefulness for cartilage study in a
rat model.
This study was supported in part by grants from the Japan Latest Osteoarthritis Society and from the Center of Excellence
Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone in Tokyo Medical and Dental University
(to T.M.), and by the Japan Society for the Promotion of Science (grant no. 18591657 to I.S.). Recombinant human bone morphogenetic
protein-2 was kindly provided by Astellas Pharma. 相似文献
44.
Epigenetic inheritance in rice plants 总被引:2,自引:0,他引:2
BACKGROUND AND AIMS: Epigenetics is defined as mechanisms that regulate gene expression without base sequence alteration. One molecular basis is considered to be DNA cytosine methylation, which reversibly modifies DNA or chromatin structures. Although its correlation with epigenetic inheritance over generations has been circumstantially shown, evidence at the gene level has been limited. The present study aims to find genes whose methylation status directly correlates with inheritance of phenotypic changes. METHODS: DNA methylation in vivo was artificially reduced by treating rice (Oryza sativa ssp. japonica) seeds with 5-azadeoxycytidine, and the progeny were cultivated in the field for > 10 years. Genomic regions with changed methylation status were screened by the methylation-sensitive amplified polymorphysm (MSAP) method, and cytosine methylation was directly scanned by the bisulfite mapping method. Pathogen infection with Xanthomonas oryzae pv. oryzae, race PR2 was performed by the scissors-dip method on mature leaf blades. KEY RESULTS: The majority of seedlings were lethal, but some survived to maturity. One line designated as Line-2 showed a clear marker phenotype of dwarfism, which was stably inherited by the progeny over nine generations. MSAP screening identified six fragments, among which two were further characterized by DNA blot hybridization and direct methylation mapping. One clone encoding a retrotransposon gag-pol polyprotein showed a complete erasure of 5-methylcytosines in Line-2, but neither translocation nor expression of this region was detectable. The other clone encoded an Xa21-like protein, Xa21G. In wild-type plants, all cytosines were methylated within the promoter region, whereas in Line-2, corresponding methylation was completely erased throughout generations. Expression of Xa21G was not detectable in wild type but was constitutive in Line-2. When infected with X. oryzae pv. oryzae, against which Xa21 confers resistance in a gene-for-gene manner, the progeny of Line-2 were apparently resistant while the wild type was highly susceptible without Xa21G expression. CONCLUSIONS: These results indicated that demethylation was selective in Line-2, and that promoter demethylation abolished the constitutive silencing of Xa21G due to hypermethylation, resulting in acquisition of disease resistance. Both hypomethylation and resistant trait were stably inherited. This is a clear example of epigenetic inheritance, and supports the idea of Lamarckian inheritance which suggested acquired traits to be heritable. 相似文献
45.
Akimoto Y Hart GW Wells L Vosseller K Yamamoto K Munetomo E Ohara-Imaizumi M Nishiwaki C Nagamatsu S Hirano H Kawakami H 《Glycobiology》2007,17(2):127-140
Many nuclear and cytoplasmic proteins are O-glycosylated on serine or threonine residues with the monosaccharide beta-N-acetylglucosamine, which is then termed O-linked N-acetylglucosamine (O-GlcNAc). It has been shown that abnormal O-GlcNAc modification (O-GlcNAcylation) of proteins is one of the causes of insulin resistance and diabetic complications. In this study, in order to examine the relationship between O-GlcNAcylation of proteins and glucose-stimulated insulin secretion in noninsulin-dependent type (type 2) diabetes, we investigated the level of O-GlcNAcylation of proteins, especially that of PDX-1, and the expression of O-GlcNAc transferase in Goto-Kakizaki (GK) rats, which are an animal model of type-2 diabetes. By immunoblot and immunohistochemical analyses, the expression of O-GlcNAc transferase protein and O-GlcNAc-modified proteins in whole pancreas and islets of Langerhans of 15-week-old diabetic GK rats and nondiabetic Wistar rats was examined. The expression of O-GlcNAc transferase at the protein level and O-GlcNAc transferase activity were increased significantly in the diabetic pancreas and islets. The diabetic pancreas and islets also showed an increase in total cellular O-GlcNAc-modified proteins. O-GlcNAcylation of PDX-1 was also increased. In the diabetic GK rats, significant increases in the immunoreactivities of both O-GlcNAc and O-GlcNAc transferase were observed. PUGNAc, an inhibitor of O-GlcNAcase, induced an elevation of O-GlcNAc level and a decrease of glucose-stimulated insulin secretion in isolated islets. These results indicate that elevation of the O-GlcNAcylation of proteins leads to deterioration of insulin secretion in the pancreas of diabetic GK rats, further providing evidence for the role of O-GlcNAc in the insulin secretion. 相似文献
46.
47.
Shimizu K Aizawa K Suzuki N Masuchi K Okada H Akimoto T Mesaki N Kono I Akama T 《Journal of strength and conditioning research / National Strength & Conditioning Association》2011,25(7):1943-1950
The purpose of this study was to examine weight loss effects on immune function in judo athletes. Six elite male Japanese judo athletes (20.3 ± 0.4 years) were enrolled in this study. They completed usual weight loss programs during 2 weeks preceding an actual competition. Subjects noted the appearance of upper-respiratory tract infection (URTI) symptoms during the study period. Blood samples were obtained at 40 (baseline period: BL) and 3 (weight loss period: WL) days before and 1 day after the competition (AC). The CD3, CD4, CD8, CD56CD3, CD28CD4, CD28CD8, and Toll-like-receptor-4 (TLR-4) CD14 cells were counted by using flow cytometer analysis. The 6 subjects reported 1 headache, 3 runny nose conditions, and 1 coughing instance during the WL. The CD3, CD4, CD8, and CD28CD4 cell counts were significantly lower at WL than at BL (p ≤ 0.05); they reverted to the baseline value at AC. The TLR-4CD14 cells were significantly fewer at WL (p ≤ 0.05); they remained fewer than they had been at BL, even at AC. These results suggest that 2 weeks of weight loss before a competition can impair cell-mediated immune function and induce high susceptibility to URTI in judo athletes. Coaches, support staff, and athletes should monitor athletes' weight loss, hydration status, appearance of URTI symptoms, and immunocompetence such as lymphocytes and monocytes to prevent the physical condition from becoming worse. 相似文献
48.
Fisher DJ Miyamoto K Harrison B Akimoto S Sarker MR McClane BA 《Molecular microbiology》2005,56(3):747-762
Clostridium perfringens type A isolates carrying an enterotoxin (cpe) gene are an important cause of human gastrointestinal diseases, including food poisoning, antibiotic-associated diarrhoea (AAD) and sporadic diarrhoea (SD). Using polymerase chain reaction (PCR), the current study determined that the cpb2 gene encoding the recently discovered beta2 toxin is present in <15% of food poisoning isolates, which typically carry a chromosomal cpe gene. However, >75% of AAD/SD isolates, which usually carry a plasmid cpe gene, tested cpb2(+) by PCR. Western blot analysis demonstrated that >97% of those cpb2(+)/cpe(+) AAD/SD isolates can produce CPB2. Additional PCR analyses, sequencing studies and pulsed field gel electrophoresis experiments determined that AAD/SD isolates carry cpb2 and cpe on the same plasmid when IS1151 sequences are present downstream of cpe, but cpb2 and cpe are located on different plasmids in AAD/SD isolates where IS1470-like sequences are present downstream of cpe. Those analyses also demonstrated that two different CPB2 variants (named CPB2h1 or CPB2h2) can be produced by AAD/SD isolates, dependent on whether IS1470-like or IS1151 sequences are present downstream of their cpe gene. CPB2h1 is approximately 10-fold more cytotoxic for CaCo-2 cells than is CPB2h2. Collectively, these results suggest that CPB2 could be an accessory toxin in C. perfringens enterotoxin (CPE)-associated AAD/SD. 相似文献
49.
Sato Y Yokoyama A Shibata K Akimoto Y Ogino S Nodasaka Y Kohgo T Tamura K Akasaka T Uo M Motomiya K Jeyadevan B Ishiguro M Hatakeyama R Watari F Tohji K 《Molecular bioSystems》2005,1(2):176-182
Carbon nanotubes (CNTs) are single- or multi-cylindrical graphene structures that possess diameters of a few nanometers, while the length can be up to a few micrometers. These could have unusual toxicological properties, in that they share intermediate morphological characteristics of both fibers and nanoparticles. To date, no detailed study has been carried out to determine the effect of length on CNT cytotoxicity. In this paper, we investigated the activation of the human acute monocytic leukemia cell line THP-1 in vitro and the response in subcutaneous tissue in vivo to CNTs of different lengths. We used 220 nm and 825 nm-long CNT samples for testing, referred to as "220-CNTs" and "825-CNTs", respectively. 220-CNTs and 825-CNTs induced human monocytes in vitro, although the activity was significantly lower than that of microbial lipopeptide and lipopolysaccharide, and no activity appeared following variation in the length of CNTs. On the other hand, the degree of inflammatory response in subcutaneous tissue in rats around the 220-CNTs was slight in comparison with that around the 825-CNTs. These results indicated that the degree of inflammation around 825-CNTs was stronger than that around 220-CNTs since macrophages could envelop 220-CNTs more readily than 825-CNTs. However, no severe inflammatory response such as necrosis, degeneration or neutrophil infiltration in vivo was observed around both CNTs examined throughout the experimental period. 相似文献
50.
Yu J He S Friedman JS Akimoto M Ghosh D Mears AJ Hicks D Swaroop A 《The Journal of biological chemistry》2004,279(40):42211-42220