全文获取类型
收费全文 | 185篇 |
免费 | 5篇 |
出版年
2023年 | 2篇 |
2021年 | 8篇 |
2020年 | 4篇 |
2019年 | 6篇 |
2018年 | 7篇 |
2017年 | 2篇 |
2016年 | 3篇 |
2015年 | 3篇 |
2014年 | 11篇 |
2013年 | 11篇 |
2012年 | 17篇 |
2011年 | 19篇 |
2010年 | 13篇 |
2009年 | 5篇 |
2008年 | 15篇 |
2007年 | 13篇 |
2006年 | 7篇 |
2005年 | 4篇 |
2004年 | 11篇 |
2002年 | 9篇 |
2001年 | 1篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1995年 | 1篇 |
1993年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1985年 | 1篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1973年 | 1篇 |
排序方式: 共有190条查询结果,搜索用时 15 毫秒
141.
Dawoon Jung Eun-Young Seo Jeffrey S. Owen Yoshiteru Aoi Seungcheon Yong Elena V. Lavrentyeva 《Bioscience, biotechnology, and biochemistry》2018,82(9):1624-1632
Hot springs are regarded as treasury of valuable thermophiles. Like other bacteria, thermophiles are not easily cultivated using conventional culture methods. We used an advanced cultivation method, the filter plate microbial trap (FPMT), to isolate bacteria from thermal springs. In total, 184 isolates were obtained from five thermal springs using the FPMT and standard agar plate method, and their 16S rRNA gene sequences were analyzed. FPMT allowed us to obtain a culture collection that was larger, richer, and more novel than that obtained by standard cultivation. Seven novel species were obtained using the FPMT technique, whereas only one was isolated using a standard cultivation. We also found clear differences in the patterns of phylogenetic diversity and physiological properties between isolates from two cultivation methods. The results have encouraged us to apply the FPMT method in other extreme environments and offer further support for fostering the development of new cultivation methods. 相似文献
142.
Satoru Tsuruta Norihisa Kimura Keinosuke Ishido Daisuke Kudo Kentaro Sato Tetsu Endo Tadashi Yoshizawa Aoi Sukeda Nobuyoshi Hiraoka Hiroshi Kijima Kenichi Hakamada 《World journal of surgical oncology》2018,16(1):227
Background
Calcifying nested stromal epithelial tumor (CNSET) is a primary neoplasm of the liver, characterized by well-demarcated nests consisting of spindle and epithelioid cells with calcification and bone formation. An association of Cushing syndrome with CNSET has drawn attention, but the origin of CNSET has not been clarified.Case presentation
We report here the case of a 20-year-old male with Klinefelter syndrome who underwent liver resection for an increasing liver tumor that was pathologically diagnosed with CNSET. He was postoperatively followed up and received several examinations, and recurrences and extrahepatic lymph node metastases were detected on the 64th day after surgery. Chemoembolization and chemotherapy were not effective, leading to tumor progression with development of progressive liver failure, and the patient finally died 164 days after hepatectomy.Conclusions
This case suggests that an imbalance of hormones affects the genesis and progression of CNSET, and indicates the importance of closely following patients with CNSET by imaging with attention to hepatic recurrence and extrahepatic metastases.143.
Cooperative interaction between hepatocyte nuclear factor 4 alpha and GATA transcription factors regulates ATP-binding cassette sterol transporters ABCG5 and ABCG8 总被引:3,自引:0,他引:3 下载免费PDF全文
Sumi K Tanaka T Uchida A Magoori K Urashima Y Ohashi R Ohguchi H Okamura M Kudo H Daigo K Maejima T Kojima N Sakakibara I Jiang S Hasegawa G Kim I Osborne TF Naito M Gonzalez FJ Hamakubo T Kodama T Sakai J 《Molecular and cellular biology》2007,27(12):4248-4260
Cholesterol homeostasis is maintained by coordinate regulation of cholesterol synthesis and its conversion to bile acids in the liver. The excretion of cholesterol from liver and intestine is regulated by ATP-binding cassette half-transporters ABCG5 and ABCG8. The genes for these two proteins are closely linked and divergently transcribed from a common intergenic promoter region. Here, we identified a binding site for hepatocyte nuclear factor 4alpha (HNF4alpha) in the ABCG5/ABCG8 intergenic promoter, through which HNF4alpha strongly activated the expression of a reporter gene in both directions. The HNF4alpha-responsive element is flanked by two conserved GATA boxes that were also required for stimulation by HNF4alpha. GATA4 and GATA6 bind to the GATA boxes, coexpression of GATA4 and HNF4alpha leads to a striking synergistic activation of both the ABCG5 and the ABCG8 promoters, and binding sites for HNF4alpha and GATA were essential for maximal synergism. We also show that HNF4alpha, GATA4, and GATA6 colocalize in the nuclei of HepG2 cells and that a physical interaction between HNF4alpha and GATA4 is critical for the synergistic response. This is the first demonstration that HNF4alpha acts synergistically with GATA factors to activate gene expression in a bidirectional fashion. 相似文献
144.
Campos E Façanha A Moraes J da Silva Vaz I Masuda A Logullo C 《Insect biochemistry and molecular biology》2007,37(10):1103-1107
This study describes Exopolyphosphatases (PPX) activity in mitochondria of Rhipicephalus microplus embryos. Mitochondria were isolated by differential centrifugation and PPX activity was analyzed through the hydrolysis of the substrate Polyphosphate (Poly P(15)). We investigated the influence of NADH, NAD+, Pi and ADP in a concentration range of 0.1-2.0 mM. Poly P hydrolysis was stimulated about two-fold by NADH and strongly inhibited by Pi. The PPX activity also increased in the presence of the respiratory substrates pyruvic and succinic acids, and this stimulatory effect disappeared upon addition of KCN. Mitochondrial respiration was activated by ADP using poly P as the only source of Pi. Endogenous poly P content changed following PPX activity during embryogenesis from the first up to 18th day of development. The data describe exopoly P as being modulated by Pi demand and related to energy supply during embryogenesis of hard ticks. 相似文献
145.
Iwahashi A Ishii A Yamazaki N Hashimoto M Ohkura K Kataoka M Majima E Terada H Shinohara Y 《Mitochondrion》2008,8(2):196-204
Comparison of the amino acid sequence of yeast type 2 ADP/ATP carrier (yAAC2) with that of bovine type 1 AAC (bAAC1) revealed that the N- and C-terminus of yAAC2 are 15- and 6-amino acids longer, respectively, than those of bAAC1. In the present study, we focused on the difference in the C-terminal region between yAAC2 and bAAC1. Deletion of first six residues of C-terminus of yAAC did not markedly affect the function of yAAC2; however, further deletion of 1 amino acid (7th amino acid from the C-terminus) destroyed its function. On the contrary, deletion of the first amino acid residue of the C-terminus of bAAC1 caused failure of its functional expression in yeast mitochondria. Based on these results, we concluded that the 6-amino acid residue extension of the C-terminus of yAAC2 was not necessary for the function of this carrier and that the remainder of the C-terminal region of yAAC2, having a length conserved with that of bAAC1, is important for the transport function of AACs. We next prepared various single-Cys mutants in which each of 32 residues in the C-terminus of yAAC2 was replaced by a Cys residue. Since all mutants were successfully expressed in yeast mitochondria, we examined the reactivity of these cysteine residues with the membrane-impermeable sulfhydryl reagent eosin 5-maleimide (EMA). As a result, all cysteine residues that replaced the 9 continuous amino acids in Met310-Lys318 showed high reactivity with EMA regardless of the presence of carboxyatractyloside or bongkrekic acid; and so this region was concluded to be exposed to the water-accessible environment. Furthermore, based on the reactivities of cysteine residues that replaced amino acids in the sixth transmembrane segment, the probable structural features of the C-terminal region of this carrier in the presence of bongkrekic acid were discussed. 相似文献
146.
147.
Haruna Tamano Haruna Tokoro Daichi Murakami Ryo Furuhata Satoko Nakajima Nana Saeki Misa Katahira Aoi Shioya Yukino Tanaka Mako Egawa Atsushi Takeda 《Experimental Animals》2021,70(4):514
Ninjin-yoei-to (NYT), a Kampo medicine, has ameliorative effects on cognitive dysfunction via enhancing cholinergic neuron activity. To explore an efficacy of NYT administration for prevention and cure of Alzheimer’s disease, here we examined the effect of NYT on amyloid β1-42 (Aβ1-42)-induced neurodegeneration in the dentate gyrus. A diet containing 3% NYT was administered to mice for 2 weeks and human Aβ1-42 was intracerebroventricularly injected. Neurodegeneration in the dentate granule cell layer of the hippocampus, which was determined 2 weeks after the injection, was rescued by administration of the diet for 4 weeks. Aβ staining (uptake) was not modified in the dentate granule cell layer by pre-administration of the diet for 2 weeks, while Aβ1-42-induced increase in intracellular Zn2+ was reduced, suggesting that pre-administration of NYT prior to Aβ injection is effective for reducing Aβ1-42-induced Zn2+ toxicity in the dentate gyrus. As a matter of fact, Aβ1-42-induced neurodegeneration in the dentate gyrus was rescued by pre-administration of NYT. Interestingly, the level of metallothioneins, intracellular Zn2+-binding proteins, which can capture Zn2+ from Zn-Aβ1-42 complexes, was elevated in the dentate granule cell layer by pre-administration of NYT. The present study suggests that pre-administration of NYT prevents Aβ1-42-mediated neurodegeneration in the dentate gyurs by induced synthesis of metallothioneins, which reduces intracellular Zn2+ toxicity induced by Aβ1-42. 相似文献
148.
149.
Mojgan Rastegar Akitsu Hotta Peter Pasceri Maisam Makarem Aaron Y. L. Cheung Shauna Elliott Katya J. Park Megumi Adachi Frederick S. Jones Ian D. Clarke Peter Dirks James Ellis 《PloS one》2009,4(8)
Background
Rett Syndrome (RTT) is an Autism Spectrum Disorder and the leading cause of mental retardation in females. RTT is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment. Our objective is to develop viral vectors for MECP2 gene transfer into Neural Stem Cells (NSC) and neurons suitable for gene therapy of Rett Syndrome.Methodology/Principal Findings
We generated self-inactivating (SIN) retroviral vectors with the ubiquitous EF1α promoter avoiding known silencer elements to escape stem-cell-specific viral silencing. High efficiency NSC infection resulted in long-term EGFP expression in transduced NSC and after differentiation into neurons. Infection with Myc-tagged MECP2-isoform-specific (E1 and E2) vectors directed MeCP2 to heterochromatin of transduced NSC and neurons. In contrast, vectors with an internal mouse Mecp2 promoter (MeP) directed restricted expression only in neurons and glia and not NSC, recapitulating the endogenous expression pattern required to avoid detrimental consequences of MECP2 ectopic expression. In differentiated NSC from adult heterozygous Mecp2tm1.1Bird+/− female mice, 48% of neurons expressed endogenous MeCP2 due to random inactivation of the X-linked Mecp2 gene. Retroviral MECP2 transduction with EF1α and MeP vectors rescued expression in 95–100% of neurons resulting in increased dendrite branching function in vitro. Insulated MECP2 isoform-specific lentiviral vectors show long-term expression in NSC and their differentiated neuronal progeny, and directly infect dissociated murine cortical neurons with high efficiency.Conclusions/Significance
MeP vectors recapitulate the endogenous expression pattern of MeCP2 in neurons and glia. They have utility to study MeCP2 isoform-specific functions in vitro, and are effective gene therapy vectors for rescuing dendritic maturation of neurons in an ex vivo model of RTT. 相似文献150.
Saliva of the cattle tick Boophilus microplus contains two thrombin inhibitors, BmAP and microphilin. This work presents the purification and characterization of microphilin. It was purified from the saliva by gel filtration, ultrafiltration through a 3 kDa cut-off membrane and affinity chromatography in a thrombin-Sepharose column. Analysis by mass spectrometry showed a molecular mass of 1770 Da. Microphilin is the smallest salivary thrombin inhibitor peptide known to date. It inhibits fibrinocoagulation and thrombin-induced platelet aggregation with an IC(50) of 5.5 microM, is temperature resistant and its inhibitory activity was abolished by protease K treatment. Microphilin did not inhibit the amidolytic activity of the enzyme upon a small chromogenic substrate, but inhibited the hydrolysis of a substrate that binds both catalytic site and exosite I. Therefore, we propose that microphilin blocks thrombin at exosite I. 相似文献