全文获取类型
收费全文 | 7197篇 |
免费 | 508篇 |
出版年
2021年 | 61篇 |
2019年 | 64篇 |
2018年 | 72篇 |
2017年 | 60篇 |
2016年 | 92篇 |
2015年 | 149篇 |
2014年 | 168篇 |
2013年 | 360篇 |
2012年 | 317篇 |
2011年 | 328篇 |
2010年 | 182篇 |
2009年 | 179篇 |
2008年 | 335篇 |
2007年 | 302篇 |
2006年 | 345篇 |
2005年 | 331篇 |
2004年 | 310篇 |
2003年 | 315篇 |
2002年 | 314篇 |
2001年 | 297篇 |
2000年 | 290篇 |
1999年 | 238篇 |
1998年 | 93篇 |
1997年 | 84篇 |
1996年 | 72篇 |
1995年 | 71篇 |
1994年 | 63篇 |
1993年 | 77篇 |
1992年 | 163篇 |
1991年 | 173篇 |
1990年 | 157篇 |
1989年 | 149篇 |
1988年 | 146篇 |
1987年 | 126篇 |
1986年 | 102篇 |
1985年 | 82篇 |
1984年 | 103篇 |
1983年 | 83篇 |
1982年 | 50篇 |
1981年 | 47篇 |
1980年 | 58篇 |
1979年 | 96篇 |
1978年 | 69篇 |
1977年 | 75篇 |
1976年 | 42篇 |
1975年 | 41篇 |
1974年 | 43篇 |
1973年 | 45篇 |
1972年 | 43篇 |
1968年 | 34篇 |
排序方式: 共有7705条查询结果,搜索用时 46 毫秒
991.
Kamemura K Ogawa M Ohkubo S Ohtsuka Y Shitara Y Komiya T Maeda S Ito A Yoshida M 《FEBS letters》2012,586(9):1379-1383
Mitochondria perform multiple functions critical to the maintenance of cellular homeostasis. Here we report that the downregulation of histone deacetylase 6 (HDAC6) causes a reduction in the net activity of mitochondrial enzymes, including respiratory complex II and citrate synthase. HDAC6 deacetylase and ubiquitin-binding activities were both required for recovery of reduced mitochondrial metabolic activity due to the loss of HDAC6. Hsp90, a substrate of HDAC6, localizes to mitochondria and partly mediates the regulation of mitochondrial metabolic activity by HDAC6. Our finding suggests that HDAC6 regulates mitochondrial metabolism and might serve as a cellular homeostasis surveillance factor. 相似文献
992.
Using fast-scanning atomic force microscopy, we directly visualized the interaction of Escherichia coli RNA polymerase (RNAP) with DNA at the scan rate of 1-2 frames per second. The analyses showed that the RNAP can locate the promoter region not only by sliding but also by hopping and/or segmental transfer. Upon the addition of 0.05 mM NTPs to the stalled complex, the RNAP molecule pulled the template DNA uni-directionally at the rates of 15 nucleotides/s on average. The present method is potentially applicable to examine a variety of protein-nucleic acid interactions, especially those involved in the process of gene regulation. 相似文献
993.
Yoshida S Mohamed RH Kajikawa M Koizumi J Tanaka M Fugo K Otsuka N Maenaka K Yagita H Chiba H Kasahara M 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(8):3972-3979
Dendritic epidermal T cells (DETCs) found in mouse skin are NKG2D-positive γδ T cells involved in immune surveillance and wound repair. It is assumed that the interaction of an NKG2D receptor on DETCs and an MHC class I-like NKG2D ligand on keratinocytes activates DETCs, which then secrete cytokines promoting wound repair. However, direct evidence that DETC activation through NKG2D signaling promotes wound repair is not available. In the present study, we generated mAbs for an NKG2D ligand H60c previously suggested to be expressed specifically on skin keratinocytes. Local administration of H60c-specific mAb inhibited activation of DETCs and significantly delayed wound repair. Likewise, administration of NKG2D-specific mAb impaired wound repair to a similar extent. The delay in wound closure resulting from the blockade of the NKG2D pathway was comparable to that observed in γδ T cell-deficient mice. These results indicate that H60c/NKG2D interactions play a critical role in wound repair. Reassessment of binding affinities showed that H60c monomers bind to NKG2D with affinity (K(d) = 26 ± 3.2 nM) comparable to those of other high-affinity NKG2D ligands. H60c is transcribed not only in skin but also in tissues such as tongue and female reproductive tract known to contain epithelium-resident γδ T cells expressing invariant TCRs, suggesting a more general role for H60c in the maintenance of epithelial integrity. 相似文献
994.
Fujinaga M Maeda J Yui J Hatori A Yamasaki T Kawamura K Kumata K Yoshida Y Nagai Y Higuchi M Suhara T Fukumura T Zhang MR 《Journal of neurochemistry》2012,120(1):115-124
Neurovascular degeneration contributes to the pathogenesis of Alzheimer's disease (AD). Because erythropoietin (EPO) promotes endothelial regeneration, we investigated the therapeutic effects of EPO in animal models of AD. In aged Tg2576 mice, EPO receptors (EPORs) were expressed in the cortex and hippocampus. Tg2576 mice were treated with daily injection of EPO (5000 IU/kg/day) for 5 days. At 14 days, EPO improved contextual memory as measured by fear-conditioning test. EPO enhanced endothelial proliferation and the level of synaptophysin expression in the brain. EPO also increased capillary density, and decreased the level of the receptor for advanced glycation endproducts (RAGE) in the brain, while decreasing in the amount of amyloid plaque and amyloid-β (Aβ). In cultured human endothelial cells, EPO enhanced angiogenesis and suppressed the expression of the RAGE. These results show that EPO improves memory and ameliorates endothelial degeneration induced by Aβ in AD models. This pre-clinical evidence suggests that EPO may be useful for the treatment of AD. 相似文献
995.
Yasumura M Yoshida T Lee SJ Uemura T Joo JY Mishina M 《Journal of neurochemistry》2012,121(5):705-716
Glutamate receptor (GluR) δ1 is widely expressed in the developing forebrain, whereas GluRδ2 is selectively expressed in cerebellar Purkinje cells. Recently, we found that trans-synaptic interaction of postsynaptic GluRδ2 and pre-synaptic neurexins (NRXNs) through cerebellin precursor protein (Cbln) 1 mediates excitatory synapse formation in the cerebellum. Thus, a question arises whether GluRδ1 regulates synapse formation in the forebrain. In this study, we showed that the N-terminal domain of GluRδ1 induced inhibitory presynaptic differentiation of some populations of cultured cortical neurons. When Cbln1 or Cbln2 was added to cultures, GluRδ1 expressed in HEK293T cells induced preferentially inhibitory presynaptic differentiation of cultured cortical neurons. The synaptogenic activity of GluRδ1 was suppressed by the addition of the extracellular domain of NRXN1α or NRXN1β containing splice segment 4. Cbln subtypes directly bound to the N-terminal domain of GluRδ1. The synaptogenic activity of GluRδ1 in the presence of Cbln subtypes correlated well with their binding affinities. When transfected to cortical neurons, GluRδ1 stimulated inhibitory synapse formation in the presence of Cbln1 or Cbln2. These results together with differential interactions of Cbln subtypes with NRXN variants suggest that GluRδ1 induces preferentially inhibitory presynaptic differentiation of cortical neurons by interacting with NRXNs containing splice segment 4 through Cbln subtypes. 相似文献
996.
Takahiro Wakahama Aitor Laza‐Martínez Ahmad Iskandar Bin Haji Mohd Taha Hidetoshi Okuyama Kiyohito Yoshida Kazuhiro Kogame Koichiro Awai Masanobu Kawachi Takashi Maoka Shinichi Takaichi 《Journal of phycology》2012,48(6):1392-1402
The molecular structure of the carotenoid lactoside P457, (3S,5R,6R,3′S,5′R,6′S)‐13′‐cis‐5,6‐epoxy‐3′,5′‐dihydroxy‐3‐(β‐d ‐galactosyl‐(1→4)‐β‐d ‐glucosyl)oxy‐6′,7′‐didehydro‐5,6,7,8,5′,6′‐hexahydro‐β,β‐caroten‐20‐al, was confirmed by spectroscopic methods using Symbiodinium sp. strain NBRC 104787 cells isolated from a sea anemone. Among various algae, cyanobacteria, land plants, and marine invertebrates, the distribution of this unique diglycosyl carotenoid was restricted to free‐living peridinin‐containing dinoflagellates and marine invertebrates that harbor peridinin‐containing zooxanthellae. Neoxanthin appeared to be a common precursor for biosynthesis of peridinin and P457, although neoxanthin was not found in peridinin‐containing dinoflagellates. Fucoxanthin‐containing dinoflagellates did not possess peridinin or P457; green dinoflagellates, which contain chlorophyll a and b, did not contain peridinin, fucoxanthin, or P457; and no unicellular algae containing both peridinin and P457, other than peridinin‐containing dinoflagellates, have been observed. Therefore, the biosynthetic pathways for peridinin and P457 may have been coestablished during the evolution of dinoflagellates after the host heterotrophic eukaryotic microorganism formed a symbiotic association with red alga that does not contain peridinin or P457. 相似文献
997.
Murota K Yoshida M Ishibashi N Yamazaki H Minami T 《Biological trace element research》2012,145(3):349-354
Methyl mercury is contained in fish and seafood products and is taken up into the body in food. While the central nervous
system is known as a target organ, methyl mercury also induces autoimmunity and acts as a potent immunosuppressor. The aim
of the present study is to know whether methyl mercury is directly absorbed by lymph. Conscious rats were infused with methyl
mercury (4 mg/kg) via duodenal tubing as a single pulse infusion, followed by the continuous infusion of saline, and lymphatic
fluids were continuously collected from the thoracic lymph duct every 30 min until 360 min after infusion. Mercury was detected
immediately after infusion, and total mercury contents in lymph gradually increased until 90–120 min, remained steady, and
then gradually decreased until 360 min; however, the amount of mercury collected during 330–360 min was about twofold higher
than during 0–30 min. The amount of cumulative mercury in lymph at 360 min was 1.4 μg. In contrast, blood mercury concentration
was 2.4 μg/ml 5 min after infusion, with the value at 360 min being 12.6 times higher than at 5 min. Plasma mercury concentration
was 56 ng/ml at 5 min, with hundreds of nanograms per milliliter of mercury detected until 360 min. From the present study,
it is concluded that some methyl mercury is directly absorbed by lymph and remains steady 6 h after infusion. 相似文献
998.
Hara KY Kim S Yoshida H Kiriyama K Kondo T Okai N Ogino C Fukuda H Kondo A 《Applied microbiology and biotechnology》2012,93(4):1495-1502
Glutathione is a valuable tri-peptide that is widely used in the pharmaceutical, food, and cosmetic industries. Glutathione
is produced industrially by fermentation using Saccharomyces cerevisiae, and supplementation of fermentation with several amino acids can increase intracellular GSH content. More recently, however,
focus has been given to protein as a resource for biofuel and fine chemical production. We demonstrate that expression of
a protease on the cell surface of S. cerevisiae enables the direct use of keratin and soy protein as a source of amino acids and that these substrates enhanced intracellular
GSH content. Furthermore, fermentation using soy protein also enhanced cell concentration. GSH fermentation from keratin and
to a greater extent from soy protein using protease-displaying yeast yielded greater GSH productivity compared to GSH fermentation
with amino acid supplementation. This protease-displaying yeast is potentially applicable to a variety of processes for the
bio-production of value-added chemicals from proteinaceous biomass resources. 相似文献
999.
Clustered regularly interspaced short palindromic repeats (CRISPR) confer sequence-dependent, adaptive resistance in prokaryotes against viruses and plasmids via incorporation of short sequences, called spacers, derived from foreign genetic elements. CRISPR loci are thus considered to provide records of past infections. To describe the host-parasite (i.e., cyanophages and plasmids) interactions involving the bloom-forming freshwater cyanobacterium Microcystis aeruginosa, we investigated CRISPR in four M. aeruginosa strains and in two previously sequenced genomes. The number of spacers in each locus was larger than the average among prokaryotes. All spacers were strain specific, except for a string of 11 spacers shared in two closely related strains, suggesting diversification of the loci. Using CRISPR repeat-based PCR, 24 CRISPR genotypes were identified in a natural cyanobacterial community. Among 995 unique spacers obtained, only 10 sequences showed similarity to M. aeruginosa phage Ma-LMM01. Of these, six spacers showed only silent or conservative nucleotide mutations compared to Ma-LMM01 sequences, suggesting a strategy by the cyanophage to avert CRISPR immunity dependent on nucleotide identity. These results imply that host-phage interactions can be divided into M. aeruginosa-cyanophage combinations rather than pandemics of population-wide infectious cyanophages. Spacer similarity also showed frequent exposure of M. aeruginosa to small cryptic plasmids that were observed only in a few strains. Thus, the diversification of CRISPR implies that M. aeruginosa has been challenged by diverse communities (almost entirely uncharacterized) of cyanophages and plasmids. 相似文献
1000.
Hojo F Sato D Matsuo J Miyake M Nakamura S Kunichika M Hayashi Y Yoshida M Takahashi K Takemura H Kamiya S Yamaguchi H 《Applied and environmental microbiology》2012,78(15):5247-5257
When Tetrahymena ciliates are cultured with Legionella pneumophila, the ciliates expel bacteria packaged in free spherical pellets. Why the ciliates expel these pellets remains unclear. Hence, we determined the optimal conditions for pellet expulsion and assessed whether pellet expulsion contributes to the maintenance of growth and the survival of ciliates. When incubated with environmental L. pneumophila, the ciliates expelled the pellets maximally at 2 days after infection. Heat-killed bacteria failed to produce pellets from ciliates, and there was no obvious difference in pellet production among the ciliates or bacterial strains. Morphological studies assessing lipid accumulation showed that pellets contained tightly packed bacteria with rapid lipid accumulation and were composed of the layers of membranes; bacterial culturability in the pellets rapidly decreased, in contrast to what was seen in ciliate-free culture, although the bacteria maintained membrane integrity in the pellets. Furthermore, ciliates newly cultured with pellets were maintained and grew vigorously compared with those without pellets. In contrast, a human L. pneumophila isolate killed ciliates 7 days postinfection in a Dot/Icm-dependent manner, and pellets harboring this strain did not support ciliate growth. Also, pellets harboring the human isolate were resuscitated by coculturing with amoebae, depending on Dot/Icm expression. Thus, while ciliates expel pellet-packaged environmental L. pneumophila for stockpiling food, the pellets packaging the human isolate are harmful to ciliate survival, which may be of clinical significance. 相似文献