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排序方式: 共有165条查询结果,搜索用时 15 毫秒
31.
Katsuma S Kobayashi J Koyano Y Matsuda-Imai N Kang W Shimada T 《Journal of virology》2012,86(5):2545-2555
Lepidopteran nucleopolyhedroviruses (NPVs) show distinct tissue tropism in host insect larvae. However, the molecular mechanism of this tropism is largely unknown. We quantitatively investigated NPV tissue tropism by measuring mRNA levels of viral genes in 16 tissues from Bombyx mori NPV (BmNPV)-infected B. mori larvae and found clear tissue tropism, i.e., BmNPV replicates poorly in the silk glands, midgut, and Malpighian tubule compared with other larval tissues. We next identified the viral genes determining tissue tropism in NPV infection by investigating the phenotypes of larvae infected with 44 BmNPV mutants in which one gene was functionally disrupted by a LacZ cassette insertion. We found that occlusion body (OB) production was markedly enhanced compared with that of the wild type in the middle silk glands (MSGs) of larvae infected with three mutants in which one of three tandemly arrayed genes (Bm7, Bm8, and Bm9) was disrupted. We generated additional mutants in which one or two genes of this gene cluster were partially deleted and showed that Bm8, also known as BV/ODV-E26, was solely required for the suppression of OB production in the MSGs of BmNPV-infected B. mori larvae. Western blotting showed that a LacZ cassette insertion in Bm7 or Bm9 resulted in aberrant expression of Bm8, presumably leading to abnormal OB production in the MSGs. Larval bioassays also revealed that disruption of Bm8 accelerated the death of B. mori larvae. These results suggest that the group I NPV-specific protein BV/ODV-E26 determines tissue tropism and virulence in host lepidopteran insects. 相似文献
32.
Naohisa Wada Hideaki Fujii Koji Koyano Shigeto Hirayama Takashi Iwai Toru Nemoto Hiroshi Nagase 《Bioorganic & medicinal chemistry letters》2012,22(24):7551-7554
Novel double-capped triplet drugs, which have one pharmacophore unit and two epoxymethano or dimethylepoxymethano structures (termed cap or diMe-cap structures, respectively) were synthesized. Key intermediate oxazoline 16 derived from acetone enabled the effective synthesis of double-capped triplets. SYK-134 (7a) and SYK-135 (8a) with N-cyclopropylmethyl substituent and cap structures showed selectivities for the κ opioid receptor. On the other hand, the N-Me series exhibited selectivities for the μ opioid receptor. The double-capped triplet drugs with diMe-cap structures preferred the μ receptor independently of their N-substituents. SYK-385 (19b), one of the μ-selective double-capped triplet drugs, showed the highest selectivity for the μ receptor among the reported μ-selective nonpeptide ligands. 相似文献
33.
Hiroyuki Kikuchi Takashi Ohtsuki Takashi Koyano Thaworn Kowithayakorn Toshiyuki Sakai Masami Ishibashi 《Bioorganic & medicinal chemistry》2009,17(3):1181-1186
Death receptor 5 (DR5) is an apoptosis-inducing membrane receptor for TNF-related apoptosis-inducing ligand (TRAIL). On screening for compounds that enhance DR5 expression using a luciferase assay with DLD-1/SacI, we previously identified 4′-demethyltoxicarol isoflavone (1) isolated from the leaves of Millettia brandisiana. In this study, we revealed that 1 sensitized TRAIL-resistant human gastric adenocarcinoma (AGS) cells to TRAIL-induced apoptosis by up-regulating the expression of DR5. 1 induced DR5 expression at both the mRNA and protein level. A human recombinant DR5/Fc chimera remarkably inhibited 1-induced apoptosis. These results suggest that the enhancement of DR5 expression by 1 was critical to the cell death. Furthermore, a MeOH extract of the bark of Ardisia colorata markedly enhanced DR5 activity in this screening system. Bioassay-guided fractionation of A. colorata led to the isolation and identification of a new isoflavone, coloratanin A (3), together with ten known compounds. The chemical structure of the new compound was elucidated on the basis of a spectroscopic analysis. 相似文献
34.
Tadayuki Yamaguchi Satoru Koyano Katsuji Yoshioka Nobuhiko Takamatsu 《Cell biology international》2009,33(3):364-368
The mitogen-activated protein kinase (MAPK) cascades, including c-Jun N-terminal kinase (JNK), are composed of a MAPK, MAPK kinase (MAPKK), and MAPKK kinase (MAPKKK). Previously, we reported that JNK-binding protein 1 (JNKBP1) enhances JNK activation induced by the TGF-β-activated kinase1 (TAK1) MAPKKK in transfected cells. We have investigated whether JNKBP1 functions as an adaptor protein for nuclear factor (NF)-κB activation mediated by TAK1 in COS-7 cells. Co-expression experiments showed that JNKBP1 interacted with not only TAK1, but also with its upstream regulators, TNF-receptor associated factors 2 and 6 (TRAF2 and TRAF6). An endogenous interaction between JNKBP1 and TRAF2 or TAK1 was confirmed by immunoprecipitation analysis. We also found that JNKBP1 could enhance the NF-κB activation induced by TAK1 and TRAF2, and could promote TRAF2 polyubiquitination. These results suggest a scaffolding role for JNKBP1 in the TRAF2-TAK1-NF-κB signaling pathway. 相似文献
35.
Hiroki Nishii Takashi Chiba Kenji Morikami Takaaki A. Fukami Hiroshi Sakamoto Kwangseok Ko Hiroshi Koyano 《Bioorganic & medicinal chemistry letters》2010,20(4):1405-1409
A novel quinoline derivative that selectively inhibits c-Met kinase was identified. The molecular design is based on a result of the analysis of a PF-2341066 (1)/c-Met cocrystal structure (PDB code: 2wgj). The kinase selectivity of the derivatives is discussed from the view point of the sequence homology of the kinases, the key interactions found in X-ray cocrystal structures, and the structure–activity relationship (SAR) obtained in this work. 相似文献
36.
Ana Cecilia AX De-Oliveira Renato S Carvalho Flavio HM Paixão Hellen S Tavares Luciana S Gueiros Carolina M Siqueira Francisco JR Paumgartten 《Malaria journal》2010,9(1):1-17
Background
The mechanisms by which malaria up and down-regulates CYP activities are not understood yet. It is also unclear whether CYP activities are modulated during non-lethal malaria infections. This study was undertaken to evaluate the time course of CYP alterations in lethal (Plasmodium berghei ANKA) and non-lethal (Plasmodium chabaudi chabaudi) murine malaria. Additionally, hypotheses on the association of CYP depression with enhanced nitric oxide (NO) production, and of CYP2a5 induction with endoplasmic reticulum dysfunction, enhanced haem metabolism and oxidative stress were examined as well.Methods
Female DBA-2 and C57BL/6 mice were infected with P.berghei ANKA or P. chabaudi and killed at different post-infection days. Infection was monitored by parasitaemia rates and clinical signs. NO levels were measured in the serum. Activities of CYP1a (ethoxyresorufin-O-deethylase), 2b (benzyloxyresorufin-O-debenzylase), 2a5 (coumarin-7-hydroxylase) and uridine-diphosphoglucuronyl-transferase (UGT) were determined in liver microsomes. Glutathione-S-transferase (GST) activity and concentrations of gluthatione (GSH) and thiobarbituric acid-reactive substances (TBARS) were determined in the liver. Levels of glucose-regulated protein 78 (GRP78) were evaluated by immunoblotting, while mRNAs of haemoxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) were determined by quantitative RT-PCR.Results
Plasmodium berghei depressed CYP1a and 2b and induced 2a5 in DBA-2 mice. In P.berghei-infected C57BL/6 mice CYP activities remained unaltered. In both strains, GST and UGT were not affected by P.berghei. Plasmodium c. chabaudi depressed CYP1a and 2b and induced 2a5 activities on the day of peak parasitaemia or near this day. CYP2a5 induction was associated with over-expression of HO-1 and enhanced oxidative stress, but it was not associated with GRP78 induction, a marker of endoplasmic reticulum stress. Plasmodium chabaudi increased serum NO on days near the parasitaemia peak in both strains. Although not elevating serum NO, P.berghei enhanced iNOS mRNA expression in the liver.Conclusion
Down-regulation of CYP1a and 2b and induction of 2a5 occurred in lethal and non-lethal infections when parasitaemia rates were high. A contribution of NO for depression of CYP2b cannot be ruled out. Results were consistent with the view that CYP2a5 and HO-1 are concurrently up-regulated and suggested that CYP2a5 induction may occur in the absence of enhanced endoplasmic reticulum stress. 相似文献37.
Takashi Ohtsuki Takashi Miyagawa Takashi Koyano Thaworn Kowithayakorn Masami Ishibashi 《Phytochemistry letters》2010,3(2):88-92
Three flavonoid glycosides including a new one, 7,4′-dimethyl-apigenin-6-C-β-glucopyranosyl-2″-O-α-l-arabinopyranoside (1) were isolated from the leaves of Solanum verbascifolium (Solanaceae) through bioassay-guided isolation. The chemical structure of 1 was established on the basis of spectroscopic analysis. TRAIL-resistance-overcoming activity of 1 was evaluated. 相似文献
38.
Characterization of entry mechanisms of human herpesvirus 8 by using an Rta-dependent reporter cell line 总被引:6,自引:0,他引:6
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To analyze the mechanisms of entry of human herpesvirus 8 (HHV-8), we established a reporter cell line T1H6 that contains the lacZ gene under the control of the polyadenylated nuclear RNA promoter, known to be strongly activated by a viral transactivator, Rta. We found that infection with cell-free virus, as well as cocultivation with HHV-8-positive primary effusion lymphoma cell lines, activated the lacZ gene of T1H6 in a sensitive and dose-dependent manner. Addition of Polybrene and centrifugation enhanced, but polysulfonate compounds inhibited, the HHV-8 infectivity. RGD-motif-containing polypeptides and integrins did not decrease the infectivity, suggesting the presence of an additional cellular receptor other than the reported one. The entry was dependent on pH acidification but not on the clathrin pathway. Although conditioned media obtained from human immunodeficiency virus (HIV)-infected cells did not have any effect on the early steps of HHV-8 infection, intracellular expression of a proviral HIV type 1, but not of Tat alone, increased the HHV-8-dependent reporter activation slightly, suggesting a potential of HIV-mediated enhancement of an early step of HHV-8 infection. 相似文献
39.
40.
Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis
van der Helm-van Mil AH Verpoort KN Breedveld FC Toes RE Huizinga TW 《Arthritis research & therapy》2005,7(5):R949-R958
Antibodies to citrullinated proteins (anti-cyclic-citrullinated peptide [anti-CCP] antibodies) are highly specific for rheumatoid
arthritis (RA) and precede the onset of disease symptoms, indicating a pathogenetic role for these antibodies in RA. We recently
showed that distinct genetic risk factors are associated with either anti-CCP-positive disease or anti-CCP-negative disease.
These data are important as they indicate that distinct pathogenic mechanisms are underlying anti-CCP-positive disease or
anti-CCP-negative disease. Likewise, these observations raise the question of whether anti-CCP-positive RA and anti-CCP-negative
RA are clinically different disease entities. We therefore investigated whether RA patients with anti-CCP antibodies have
a different clinical presentation and disease course compared with patients without these autoantibodies. In a cohort of 454
incident patients with RA, 228 patients were anti-CCP-positive and 226 patients were anti-CCP-negative. The early symptoms,
tender and swollen joint count, and C-reactive protein level at inclusion, as well as the swollen joint count and radiological
destruction during 4 years of follow-up, were compared for the two groups. There were no differences in morning stiffness,
type, location and distribution of early symptoms, patients' rated disease activity and C-reactive protein at inclusion between
RA patients with and without anti-CCP antibodies. The mean tender and swollen joint count for the different joints at inclusion
was similar. At follow-up, patients with anti-CCP antibodies had more swollen joints and more severe radiological destruction.
Nevertheless, the distribution of affected joints, for swelling, bone erosions and joint space narrowing, was similar. In
conclusion, the phenotype of RA patients with or without anti-CCP antibodies is similar with respect to clinical presentation
but differs with respect to disease course. 相似文献