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261.
Identification of the RsmG methyltransferase target as 16S rRNA nucleotide G527 and characterization of Bacillus subtilis rsmG mutants
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Nishimura K Johansen SK Inaoka T Hosaka T Tokuyama S Tahara Y Okamoto S Kawamura F Douthwaite S Ochi K 《Journal of bacteriology》2007,189(16):6068-6073
The methyltransferase RsmG methylates the N7 position of nucleotide G535 in 16S rRNA of Bacillus subtilis (corresponding to G527 in Escherichia coli). Disruption of rsmG resulted in low-level resistance to streptomycin. A growth competition assay revealed that there are no differences in fitness between the rsmG mutant and parent strains under the various culture conditions examined. B. subtilis rsmG mutants emerged spontaneously at a relatively high frequency, 10(-6). Importantly, in the rsmG mutant background, high-level-streptomycin-resistant rpsL (encoding ribosomal protein S12) mutants emerged at a frequency 200 times greater than that seen for the wild-type strain. This elevated frequency in the emergence of high-level streptomycin resistance was facilitated by a mutation pattern in rpsL more varied than that obtained by selection of the wild-type strain. 相似文献
262.
Hosaka Y Iwata M Kamiya N Yamada M Kinoshita K Fukunishi Y Tsujimae K Hibino H Aizawa Y Inanobe A Nakamura H Kurachi Y 《Channels (Austin, Tex.)》2007,1(3):198-208
Chemicals and toxins are useful tools to elucidate the structure-function relationship of various proteins including ion channels. The HERG channel is blocked by many compounds and this may cause life-threatening cardiac arrhythmia. Besides block, some chemicals such as the class III anti-arrhythmic agent nifekalant stimulate HERG at low potentials by shifting its activation curve towards hyperpolarizing voltages. This is called "facilitation". Here, we report mutations and simulations analyzing the association between nifekalant and channel pore residues for block and facilitation. Alanine-scanning mutagenesis was performed in the pore region of HERG. The mutations at the base of the pore helix (T623A), the selectivity filter (V625A) and the S6 helix (G648A, Y652A and F656A) abolished and S624A attenuated both block and facilitation induced by the drug. On the other hand, the mutation of other residues caused either an increase or a decrease in nifekalant-induced facilitation without affecting block. An open-state homology model of the HERG pore suggested that T623, S624, Y652 and F656 faced the central cavity, and were positioned within geometrical range for the drug to be able to interact with all of them at the same time. Of these, S649 was the only polar residue located within possible interaction distance from the drug held in its blocking position. Further mutations and flexible-docking simulations suggest that the size, but not the polarity, of the side chain at S649 is critical for drug induced facilitation. 相似文献
263.
Le Thi Kim Chung Toshio Hosaka Masaki Yoshida Hiroshi Sakaue Yutaka Nakaya 《Biochemical and biophysical research communications》2009,390(3):613-618
Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist that has been used as a drug injected subcutaneously for treatment of type 2 diabetes. Many studies have revealed molecular targets of Ex-4, but its influence on adipokines has not been determined. Our study showed that Ex-4 induced secretion of adiponectin into the culture medium of 3T3-L1 adipocytes. This effect of Ex-4 is due to increased adiponectin mRNA level through the GLP-1R. Both forskolin and 3-isobutyl-1-methylxanthine (IBMX), which may finally elevate cyclic adenosine monophosphate (cAMP) concentration, prevented the induction of adiponectin expression by Ex-4. Moreover, H89, a protein kinase A inhibitor, blocked the effect of Ex-4 on adiponectin. On the other hand, Ex-4 decreased the mRNA levels of inflammatory adipokines. The results indicate that Ex-4 directly promotes adiponectin secretion via the protein kinase A pathway in 3T3-L1 adipocytes and may ameliorate insulin resistance. 相似文献
264.
Teruyuki Nishimura Tomoharu Iino Morihiro Mitsuya Makoto Bamba Hitomi Watanabe Daisuke Tsukahara Kenji Kamata Kaori Sasaki Sumika Ohyama Hideka Hosaka Mayumi Futamura Yasufumi Nagata Jun-ichi Eiki 《Bioorganic & medicinal chemistry letters》2009,19(5):1357-1360
The identification and structure–activity-relationships (SARs) of novel 2-amino benzamide glucokinase activators are described. Compounds in this series were developed to be potent GK activators, and their binding mode to the GK protein was determined by crystal structure analysis. In vivo pharmacokinetic and acute in vivo efficacy studies of compound 18 are also described. 相似文献
265.
Global Conformational Change Associated with the Two-step Reaction Catalyzed by Escherichia coli Lipoate-Protein Ligase A 总被引:1,自引:0,他引:1
Kazuko Fujiwara Nobuo Maita Harumi Hosaka Kazuko Okamura-Ikeda Atsushi Nakagawa Hisaaki Taniguchi 《The Journal of biological chemistry》2010,285(13):9971-9980
Lipoate-protein ligase A (LplA) catalyzes the attachment of lipoic acid to lipoate-dependent enzymes by a two-step reaction: first the lipoate adenylation reaction and, second, the lipoate transfer reaction. We previously determined the crystal structure of Escherichia coli LplA in its unliganded form and a binary complex with lipoic acid (Fujiwara, K., Toma, S., Okamura-Ikeda, K., Motokawa, Y., Nakagawa, A., and Taniguchi, H. (2005) J Biol. Chem. 280, 33645–33651). Here, we report two new LplA structures, LplA·lipoyl-5′-AMP and LplA·octyl-5′-AMP·apoH-protein complexes, which represent the post-lipoate adenylation intermediate state and the pre-lipoate transfer intermediate state, respectively. These structures demonstrate three large scale conformational changes upon completion of the lipoate adenylation reaction: movements of the adenylate-binding and lipoate-binding loops to maintain the lipoyl-5′-AMP reaction intermediate and rotation of the C-terminal domain by about 180°. These changes are prerequisites for LplA to accommodate apoprotein for the second reaction. The Lys133 residue plays essential roles in both lipoate adenylation and lipoate transfer reactions. Based on structural and kinetic data, we propose a reaction mechanism driven by conformational changes. 相似文献
266.
Naoki Hosaka Wenhao Cui Yuming Zhang Takashi Takaki Muneo Inaba Susumu Ikehara 《Cancer immunology, immunotherapy : CII》2010,59(7):1121-1130
Thymic function decreases in line with tumor progression in patients with cancer, resulting in immunodeficiency and a poor
prognosis. In the present study, we attempted to restore thymic function by BALB/c (H-2d) syngeneic (Syn), or B6 (H-2b) allogeneic (Allo) bone marrow transplantation (BMT) using intra-bone marrow–bone marrow transplantation (IBM–BMT) plus Syn-,
Allo- or C3H (H-2k) 3rd-party fetal thymus transplantation (TT). Although the BALB/c mice with advanced tumors (Meth-A sarcoma; H-2d, >4 cm2) treated with either Syn- or Allo-BMT alone showed a slight improvement in survival compared with non-treated controls, the
mice treated with BMT + TT showed a longer survival. The mice treated with Allo-BMT + Allo-TT or 3rd-party TT showed the longest
survival. Interestingly, although there was no difference in main tumor size among the BMT groups, lung metastasis was significantly
inhibited by Allo-BMT + Allo-TT or 3rd-party TT. Numbers of CD4+ and CD8+ T cells, Con A response, and IFN-γ production increased significantly, whereas number of Gr-1+/CD11b+ myeloid suppressor cells and the percentage of FoxP3+ cells in CD4+ T cells significantly decreased in these mice. Furthermore, there was a positive correlation between survival days and the
number of T cells or T cell function, while there was a negative correlation between survival days and lung metastasis, the
number of Gr-1+/CD11b+ cells, or the percentage of FoxP3+ cells. These results suggest that BMT + TT, particularly Allo-BMT + Allo-TT or 3rd-party TT, is most effective in prolonging
survival as a result of the restoration of T cell function in hosts with advanced tumors. 相似文献
267.
C Furihata Y Sato M Hosaka T Matsushima F Furukawa M Takahashi 《Biochemical and biophysical research communications》1984,121(3):1027-1032
A sensitive method is described that detects an alteration in the structure of tRNA that is caused by cadmium but not by magnesium or zinc ions. The chromatographic system, RPC-5, separates Drosophila tyrosyl-tRNA into two fractions. These two isoacceptors differ by a single position in the anticodon where either a guanosine or queuine resides. Cadmium ions apparently interact with the tRNA and prevent the chromatographic separation. This is the first instance where cadmium is shown to cause a selective change in nucleic acid structure. The RPC-5 system seems to be uniquely useful in detecting such a change. 相似文献
268.
K. Hosaka R. E. Hanneman Jr. 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1988,76(2):172-176
Summary By using restriction enzyme analysis of chloroplast DNA, a geographical cline from the Andean region to coastal Chile was found for the tetraploid potato (Solanum tuberosum). This supports the Andean origin of Chilean ssp. tuberosum. One of the relic cultivars of the early introduction of potato to Europe had ssp. andigena type chloroplast DNA. Its derivatives were largely lost in the mid-19th century due to the late blight epidemic and were replaced by ssp. tuberosum originally introduced from Chile. Therefore, the present common potato has the same type chloroplast DNA as Chilean ssp. tuberosum. 相似文献
269.
M Kumada Y Hosaka M Kawabata H Asahi K Kato T Kobayakawa S Hayashi 《Japanese journal of medical science & biology》1987,40(2):89-93
To learn the possible alteration of immune response, hemolytic plaque-forming cells (PFC) produced in the spleen of Schistosoma japonicum infected mice treated with Praziquantel and untreated group were counted. There was no significant difference in the immunesuppression percentage between the treated and untreated groups 1 and 3 weeks after treatment. In 5 weeks after treatment, however, the immunesuppression percentage in the treated mice was markedly reduced in comparison with that of the untreated group. Recovery from immunesuppression appears to be associated with elimination or impairment of adult worms. 相似文献
270.