全文获取类型
收费全文 | 240篇 |
免费 | 13篇 |
出版年
2024年 | 1篇 |
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 1篇 |
2019年 | 4篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 4篇 |
2014年 | 15篇 |
2013年 | 8篇 |
2012年 | 8篇 |
2011年 | 15篇 |
2010年 | 14篇 |
2009年 | 8篇 |
2008年 | 9篇 |
2007年 | 15篇 |
2006年 | 13篇 |
2005年 | 12篇 |
2004年 | 10篇 |
2003年 | 14篇 |
2002年 | 11篇 |
2001年 | 8篇 |
2000年 | 14篇 |
1999年 | 9篇 |
1998年 | 6篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 4篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有253条查询结果,搜索用时 15 毫秒
31.
Fujii H Osa Y Ishihara M Hanamura S Nemoto T Nakajima M Hasebe K Mochizuki H Nagase H 《Bioorganic & medicinal chemistry letters》2008,18(18):4978-4981
Selective ring opening reaction of the N-cyclopropylmethyl group in naltrexone (1d) was effected in the presence of platinum (IV) oxide and hydrobromic acid under a hydrogen atmosphere at rt to selectively afford N-isobutyl derivative 10. The binding affinity of N-i-Bu derivative 10 for opioid receptors was 11-17 times less than that of the corresponding N-CPM compound, naltrexone (1d). However, compound 10 showed dose-dependent analgesic effects. Contrary to expectations based on previous structure-activity relationship studies for a series of N-substituted naltrexone derivatives that compound 10 would be an opioid antagonist, 10 showed dose-dependent analgesia in the mouse acetic acid writhing test (ED(50): 5.05 mg/kg, sc), indicating it was an opioid agonist. This finding may have a great influence on the drug design of opioid agonists. 相似文献
32.
Biodegradation of five chemicals (aniline, anthracene, chlornitrophen (CNP), fenitrothion (FNT) and linear alkylbenzene sulphonate (LAS)) by aquatic bacteria in three different types of ponds was determined according to the cultivation method developed by this group. The degradability toward these chemicals was varied among the ponds, except for LAS which was decomposed well in all samples. Higher degradability towards the two agrochemicals, CNT and FNT, was found in the pond surrounded by paddy fields, whereas aniline and anthracene were decomposed more rapidly in the pond located in the industrial area. Water from the pond in the botanical garden, with the least exposure to any chemicals, exhibited the lowest degradation toward all chemicals tested. There was no significant seasonal variation in the biodegradation of chemicals in these ponds. It was deduced that biodegradability toward certain chemicals could be a result of acclimatization of the microbial community by chemical contamination present and past, suggesting the possible use of biodegradation profiles as an indicator for chemical pollution in the aquatic environment. 相似文献
33.
34.
Segregative cell division and the cytoskeleton in two species of the genus Struvea (Cladophorales,Ulvophyceae, Chlorophyta)
下载免费PDF全文
![点击此处可从《Phycological Research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Kazuo Okuda Satoko Sekida Ami Hasebe Misa Iwabuchi Mitsunobu Kamiya Tasuku Hishinuma 《Phycological Research》2016,64(4):219-229
The detailed segregative cell division (SCD) processes and changes in the arrangement of cortical microtubules and actin filaments were examined in two species of Struvea. SCD was initiated by the appearance of annular constrictions along the lateral side of a mother cell. The constrictions decreased in diameter, became thin, tubular in shape, and pinched the protoplasm of the mother cell into several protoplasmic sections. The protoplasmic sections expanded and developed into daughter cells, which appressed each other, and were arranged in a single row. Lateral branches protruded from the upper parts of the daughter cells. The protoplasm of the lateral branches was divided by secondary SCDs and was distributed amongst the new daughter cells. SCD and lateral branch formation were essential for morphogenesis in Struvea. Cortical microtubules were arranged parallel and longitudinally to the cell axis before SCD. When SCD was initiated, there was considerable undulation of the cortical microtubules and several transverse bundles appeared in the cytoplasmic zone where annular constrictions occurred. A microtubule‐disrupting drug (amiprophos methyl) inhibited SCD. Actin filaments maintained reticulate patterns before and during SCD. These results demonstrated that SCD in Struvea species was quite distinct from that in Dictyosphaeria cavernosa reported previously. 相似文献
35.
Takuya Kawanai Yukio Ago Ryo Watanabe Aya Inoue Atsuki Taruta Yusuke Onaka Shigeru Hasebe Hitoshi Hashimoto Toshio Matsuda Kazuhiro Takuma 《Neurochemical research》2016,41(10):2574-2584
Valproic acid (VPA) is a multi-target drug and an inhibitor of histone deacetylase (HDAC). We have previously demonstrated that prenatal exposure to VPA at embryonic day 12.5 (E12.5), but not at E14.5, causes autism-like behavioral abnormalities in male mouse offspring. We have also found that prenatal VPA exposure causes transient histone hyperacetylation in the embryonic brain, followed by decreased neuronal cell numbers in the prefrontal and somatosensory cortices after birth. In the present study, we examined whether prenatal HDAC inhibition affects neuronal maturation in primary mouse cortical neurons. Pregnant mice were injected intraperitoneally with VPA (500 mg/kg) and the more selective HDAC inhibitor trichostatin A (TSA; 500 µg/kg) at E12.5 or E14.5, and primary neuronal cultures were prepared from the cerebral cortices of their embryos. Prenatal exposure to VPA at E12.5, but not at E14.5, decreased total number, total length, and complexity of neuronal dendrites at 14 days in vitro (DIV). The effects of VPA weakened at 21 DIV. Exposure to TSA at E12.5, but not at E14.5, also delayed maturation of cortical neurons. In addition, real-time quantitative PCR revealed that the prenatal exposure to TSA decreased neuroligin-1 (Nlgn1), Shank2, and Shank3 mRNA levels and increased contactin-associated protein-like 2 mRNA level. The delay in neuronal maturation was also observed in Nlgn1-knockdown cells, which were transfected with Nlgn1 siRNA. These findings suggest that prenatal HDAC inhibition causes changes in gene expression of autism-related molecules linked to a delay of neuronal maturation. 相似文献
36.
37.
Proteins bearing nuclear export signals (NESs) are translocated to the cytoplasm from the nucleus mainly through the CRM1-dependent pathway. However, the NES consensus sequence remains poorly defined, and there are currently no high-throughput methods for identifying NESs. In this study, we report the development of an efficient yeast selection system for detecting nuclear export activity as well as several reliable NES consensus sequences identified using this method. Our selection system is based on the nuclear export-dependent rescue of Tys1p, an essential cytoplasmic protein that has been artificially localized to the nucleus in a haploid Delta tys1 knockout strain. A screen of a random peptide library revealed 101 distinct CRM1-dependent NESs, which were classified into six patterns according to the conserved hydrophobic spacing. By combining mutational analyses, we have defined new NES consensus sequences with more specific and redundant residues than the traditional consensus sequence, which are consistent with most experimentally confirmed NESs. These NES consensus sequences should help identify functional NESs, and our selection system can be used to identify other targeting signals or proteins imported to specific subcellular compartments. 相似文献
38.
Atsuko Ishizuya-Oka Takashi Hasebe Yun-Bo Shi 《Apoptosis : an international journal on programmed cell death》2010,15(3):350-364
During amphibian metamorphosis, the larval tissues/organs rapidly degenerate to adapt from the aquatic to the terrestrial
life. At the cellular level, a large quantity of apoptosis occurs in a spatiotemporally-regulated fashion in different organs
to ensure timely removal of larval organs/tissues and the development of adult ones for the survival of the individuals. Thus,
amphibian metamorphosis provides us a good opportunity to understand the mechanisms regulating apoptosis. To investigate this
process at the molecular level, a number of thyroid hormone (TH) response genes have been isolated from several organs of
Xenopus laevis tadpoles and their expression and functional analyses are now in progress using modern molecular and genetic technologies.
In this review, we will first summarize when and where apoptosis occurs in typical larva-specific and larval-to-adult remodeling
amphibian organs to highlight that the timing of apoptosis is different in different tissues/organs, even though all are induced
by the same circulating TH. Next, to discuss how TH spatiotemporally regulates the apoptosis, we will focus on apoptosis of
the X. laevis small intestine, one of the best characterized remodeling organs. Functional studies of TH response genes using transgenic
frogs and culture techniques have shown that apoptosis of larval epithelial cells can be induced by TH either cell-autonomously
or indirectly through interactions with extracellular matrix (ECM) components of the underlying basal lamina. Here, we propose
that multiple intra- and extracellular apoptotic pathways are coordinately controlled by TH to ensure massive but well-organized
apoptosis, which is essential for the proper progression of amphibian metamorphosis. 相似文献
39.
Sun G Hasebe T Fujimoto K Lu R Fu L Matsuda H Kajita M Ishizuya-Oka A Shi YB 《PloS one》2010,5(10):e13605
Background
The intestinal epithelium undergoes constant self-renewal throughout adult life across vertebrates. This is accomplished through the proliferation and subsequent differentiation of the adult stem cells. This self-renewal system is established in the so-called postembryonic developmental period in mammals when endogenous thyroid hormone (T3) levels are high.Methodology/Principal Findings
The T3-dependent metamorphosis in anurans like Xenopus laevis resembles the mammalian postembryonic development and offers a unique opportunity to study how the adult stem cells are developed. The tadpole intestine is predominantly a monolayer of larval epithelial cells. During metamorphosis, the larval epithelial cells undergo apoptosis and, concurrently, adult epithelial stem/progenitor cells develop de novo, rapidly proliferate, and then differentiate to establish a trough-crest axis of the epithelial fold, resembling the crypt-villus axis in the adult mammalian intestine. The leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a well-established stem cell marker in the adult mouse intestinal crypt. Here we have cloned and analyzed the spatiotemporal expression profile of LGR5 gene during frog metamorphosis. We show that the two duplicated LGR5 genes in Xenopus laevis and the LGR5 gene in Xenopus tropicalis are highly homologous to the LGR5 in other vertebrates. The expression of LGR5 is induced in the limb, tail, and intestine by T3 during metamorphosis. More importantly, LGR5 mRNA is localized to the developing adult epithelial stem cells of the intestine.Conclusions/Significance
These results suggest that LGR5-expressing cells are the stem/progenitor cells of the adult intestine and that LGR5 plays a role in the development and/or maintenance of the adult intestinal stem cells during postembryonic development in vertebrates. 相似文献40.
Activation of nucleotide‐binding domain‐like receptor containing protein 3 inflammasome in dendritic cells and macrophages by Streptococcus sanguinis
下载免费PDF全文
![点击此处可从《Cellular microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ayumi Saeki Toshihiko Suzuki Akira Hasebe Ryousuke Kamezaki Mari Fujita Futoshi Nakazawa Ken‐Ichiro Shibata 《Cellular microbiology》2017,19(3)
Streptococcus sanguinis is frequently isolated from the blood of patients with infective endocarditis and contributes to the pathology of this disease through induction of interleukin (IL)‐1β responsible for the development of the disease. However, the mechanism of IL‐1β induction remains unknown. In this study, S. sanguinis activated a murine dendritic cell (DC) to induce IL‐1β and this activity was attenuated by silencing the mRNAs of nucleotide‐binding domain‐like receptor containing protein 3 (NLRP3) and caspase‐1. S. sanguinis induced IL‐1β production in murine bone marrow‐derived macrophage, but this activity was significantly reduced in bone marrow‐derived macrophages from NLRP3‐, apoptosis‐associated speck‐like protein containing a caspase‐recruitment domain‐, and caspase‐1‐deficient mice. DC phagocytosed S. sanguinis cells, followed by the release of adenosine triphosphate (ATP). The ATP‐degradating enzyme attenuated the release of ATP and IL‐1β. The inhibitors for ATP receptor reduced IL‐1β release in DC. These results strongly suggest that S. sanguinis has the activity to induce IL‐1β through the NLRP3 inflammasome in macrophage and DC and interaction of purinergic receptors with ATP released is involved in expression of the activity. 相似文献