全文获取类型
收费全文 | 137篇 |
免费 | 11篇 |
专业分类
148篇 |
出版年
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 6篇 |
2015年 | 8篇 |
2014年 | 10篇 |
2013年 | 1篇 |
2012年 | 13篇 |
2011年 | 6篇 |
2010年 | 7篇 |
2009年 | 5篇 |
2008年 | 12篇 |
2007年 | 10篇 |
2006年 | 7篇 |
2005年 | 5篇 |
2004年 | 7篇 |
2003年 | 7篇 |
2002年 | 7篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 1篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1982年 | 1篇 |
1978年 | 1篇 |
1977年 | 2篇 |
排序方式: 共有148条查询结果,搜索用时 0 毫秒
1.
The Drosophila melanogaster gene flightless-I, involved in gastrulation and
muscle degeneration, has Caenorhabditis elegans and human homologues. In
these highly conserved genes, two previously known gene families have been
brought together, families encoding the actin- binding proteins related to
gelsolin and the leucine-rich-repeat (LRR) group of proteins involved in
protein-protein interactions. Both these gene families exhibit
characteristics of molecular changes involving replication slippage and
exon shuffling. Phylogenetic analyses of 19 amino acid sequences of 6
related protein types indicate that actin- associated proteins related to
gelsolin are monophyletic to a common ancestor and include flightless
proteins. Conversely, comparison of 24 amino acid sequences of LRR proteins
including the flightless proteins indicates that flightless proteins are
members of a structurally related subgroup. Included in the flightless
cluster are human and mouse rsp-1 proteins involved in suppressing v-Ras
transformation of cells and the membrane-associated yeast (Saccharomyces
cerevisae) adenylate cyclase whose analogous LRRs are required for
interaction with Ras proteins. There is a strong possibility that ligands
for this group could be related and that flightless may have a similar role
in Ras signal transduction. It is hypothesized that an ancestral monomeric
gelsolin precursor protein has undergone at least four independent gene
reorganization events to account for the structural diversity of the extant
family of gelsolin-related proteins and that gene duplication and exon
shuffling events occurred prior to or at the beginning of multicellular
life, resulting in the evolution of some members of the family soon after
the appearance of actin-type proteins.
相似文献
2.
M K Gordon J K Marchant J W Foley F Igoe E P Gibney H D Nah M Barembaum J C Myers E Rodriguez B Dublet M van der Rest T F Linsenmayer W B Upholt D E Birk 《Matrix biology》1999,18(5):481-486
Chicken alpha1(V) collagen cDNAs have been cloned by a variety of methods and positively identified. We present here the entire translated sequence of the chick polypeptide and compare selected regions to other collagen chains in the type V/XI family. 相似文献
3.
Kyeongah Nah Hiroshi Nishiura Naho Tsuchiya Xiaodan Sun Yusuke Asai Akifumi Imamura 《Theoretical biology & medical modelling》2017,14(1):16
The public benefit of test-and-treat has induced a need to justify goodness for the public, and mathematical modeling studies have played a key role in designing and evaluating the test-and-treat strategy for controlling HIV/AIDS. Here we briefly and comprehensively review the essence of contemporary understanding of the test-and-treat policy through mathematical modeling approaches and identify key pitfalls that have been identified to date. While the decrease in HIV incidence is achieved with certain coverages of diagnosis, care and continued treatment, HIV prevalence is not necessarily decreased and sometimes the test-and-treat is accompanied by increased long-term cost of antiretroviral therapy (ART). To confront with the complexity of assessment on this policy, the elimination threshold or the effective reproduction number has been proposed for its use in determining the overall success to anticipate the eventual elimination. Since the publication of original model in 2009, key issues of test-and-treat modeling studies have been identified, including theoretical problems surrounding the sexual partnership network, heterogeneities in the transmission dynamics, and realistic issues of achieving and maintaining high treatment coverage in the most hard-to-reach populations. To explicitly design country-specific control policy, quantitative modeling approaches to each single setting with differing epidemiological context would require multi-disciplinary collaborations among clinicians, public health practitioners, laboratory technologists, epidemiologists and mathematical modelers. 相似文献
4.
Magnesium-induced inner membrane aggregation in heart mitochondria: prevention and reversal by carboxyatractyloside and bongkrekic acid 下载免费PDF全文
Mg(2+) at an optimal concentration of 2mM (ph 6.5) induces large increases (up to 30 percent) in the optical density of bovine heart mitochondria incubated under conditions of low ionic strength (< approx. 0.01). The increases are associated with aggregation (sticking together) of the inner membranes and are little affected by changes in the energy status of the mitochondria. Virtually all of a number of other polyvalent cations tested and Ag(+) induce increases in mitochondrial optical density similar to those induced by Mg(2+), their approximate order of concentration effectiveness in respect to Mg(2+) being: La(3+) > Pb(2+) = Cu(2+) > Cd(2+) > Zn(2+) > Ag(+) > Mn(2+) > Ca(2+) > Mg(2+). With the exception of Mg(2+), all of these cations appear to induce swelling of the mitochondria concomitant with inner membrane aggregation. The inhibitors of the adenine nucleotide transport reaction carboxyatratyloside and bongkrekic acid are capable of preventing and reversing Mg(2+)-induced aggregation at the same low concentration required for complete inhibition of phosphorylating respiration, suggesting that they inhibit the aggregation by binding to the adenine nucleotide carrier. The findings are interpreted to indicate (a) that the inner mitochondrial membrane is normally prevented from aggregating by virtue of its net negative outer surface change, (b) that the cations induce the membrane to aggregate by binding at its outer surface, decreasing the net negative charge, and (c) that carboxyatractyloside and bongkrekic acid inhibit the aggregation by binding to the outer surface of the membrane, increasing the net negative charge. 相似文献
5.
We have investigated the effects of centrally administered ginsenoside Rc and Rg1 on the modulation of G protein expression in the central nervous system in rat brain. The effects of continuous infusion of ginsenosides on the modulation of G protein -subunit mRNA were investigated by using in situ hybridization study. Rats were infused with ginsenoside Rc or Rg1 (10 g/10 l/h, i.c.v.) for 7 days, through preimplanted cannula by osmotic minipumps. The level of Gs mRNA was not changed by the infusion of ginsenoside Rc or Rg1. The level of Gai mRNA was significantly elevated in frontal cortex and hippocampus following treatment with ginsenoside Rc as well as ginsenoside Rg1. However, the level of Go mRNA was significantly decreased in part of the hippocampus and cerebellum after the animals had received ginsenoside Rg1 infusion. These results suggest that prolonged infusion of ginsenosides could differentially modulate the expression of G protein -subunit mRNA in rat brain in a region-specific manner. 相似文献
6.
Kim BS Yoon KH Oh HM Choi EY Kim SW Han WC Kim EA Choi SC Kim TH Yun KJ Kim EC Lyou JH Nah YH Chung HT Cha YN Jun CD 《Cellular immunology》2002,220(2):96-106
Iron is an essential element for the neoplastic cell growth, and iron chelators have been tested for their potential anti-proliferative and cytotoxic effects. To determine the mechanism of cell death induced by iron chelators, we explored the pathways of the three structurally related mitogen-activated protein (MAP) kinase subfamilies during apoptosis induced by iron chelators. We report that the chelator deferoxamine (DFO) strongly activates both p38 MAP kinase and extracellular signal-regulated kinase (ERK) at an early stage of incubation, but slightly activates c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) at a late stage of incubation. Among three MAP kinase blockers used, however, the selective p38 MAP kinase inhibitor SB203580 could only protect HL-60 cells from chelator-induced cell death, indicating that p38 MAP kinase serves as a major mediator of apoptosis induced by iron chelator. DFO also caused release of cytochrome c from mitochondria and induced activation of caspase 3 and caspase 8. Interestingly, treatment of HL-60 cells with SB203580 greatly abolished cytochrome c release, and activation of caspase 3 and caspase 8. Collectively, the current study reveals that p38 MAP kinase plays an important role in iron chelator-mediated cell death of HL-60 cells by activating downstream apoptotic cascade that executes cell death pathway. 相似文献
7.
Kang OH Jeong HJ Kim DK Choi SC Kim TH Nah YH Kim HM Lee YM 《Cell biochemistry and function》2003,21(2):161-167
Trypsin activating both proteinase-activated receptor (PAR) 2 and PAR4 plays an important role in inflammation. We have investigated the potential of trypsin to induce TNF-alpha secretion from the human leukemic mast cell line (HMC-1). HMC-1 cells co-express both PAR2 and PAR4, and their agonist trypsin signals to HMC-1 cells. Trypsin (100 nm), SLIGKV-NH(2) (100 microm, corresponding to the PAR2 tethered ligand), or GYPGQV-NH(2) (100 microm, corresponding to the PAR4 tethered ligand) induced tumour necrosis factor (TNF)-alpha secretion from HMC-1 cells. TNF-alpha secretion by trypsin was significantly blocked by pretreatment with 50 microm PD098059, MEK-1 inhibitor. Furthermore, trypsin stimulated the activation of extracellular signal-regulated kinase (ERK) in HMC-1 cells without any detectable activation of c-Jun N-terminal kinase (JNK) and p38 MAP kinase homologue. These results show that trypsin may induce TNF-alpha secretion following activation of ERK via both PAR2 and PAR4 on HMC-1 cells. 相似文献
8.
Annexins II, V, and VI are major components of matrix vesicles (MV), i.e. particles that have the critical role of initiating the mineralization process in skeletal tissues. Furthermore, types II and X collagen are associated with MV, and these interactions mediated by annexin V stimulate Ca(2+) uptake and mineralization of MV. However, the exact roles of annexin II, V, and VI and the interaction between annexin V and types II and X collagen in MV function and initiation of mineralization are not well understood. In this study, we demonstrate that annexin II, V, or VI mediate Ca(2+) influx into phosphatidylserine (PS)-enriched liposomes, liposomes containing lipids extracted from authentic MV, and intact authentic MV. The annexin Ca(2+) channel blocker, K-201, not only inhibited Ca(2+) influx into fura-2-loaded PS-enriched liposomes mediated by annexin II, V, or VI, but also inhibited Ca(2+) uptake by authentic MV. Types II and X collagen only bound to liposomes in the presence of annexin V but not in the presence of annexin II or VI. Binding of these collagens to annexin V stimulated its Ca(2+) channel activities, leading to an increased Ca(2+) influx into the liposomes. These findings indicate that the formation of annexin II, V, and VI Ca(2+) channels in MV together with stimulation of annexin V channel activity by collagen (types II and X) binding can explain how MV are able to rapidly take up Ca(2+) and initiate the formation of the first crystal phase. 相似文献
9.
J. Hřib R. Janisch B. Vooková J. Nahálková P. Gemeiner M. Hajduch 《Biologia Plantarum》2000,43(3):329-336
The megagametophytes of the European black pine (Pinus nigra Arn.) were cultured on modified MS medium. After 10 d, protein bodies showed well-marked degradation on freeze-etched replicas and in preparations observed by scanning electron microscopy. After 20 d of cultivation, the megagametophyte cells were completely empty. Proteins secreted into the agar medium were determined by electrophoresis and 15 different proteins, in the range of 6.5 to 71 kDa, were identified. 相似文献
10.
Lee BH Jeong SM Ha TS Park CS Lee JH Kim JH Kim DH Han JS Kim HC Ko SR Nah SY 《Molecules and cells》2004,18(1):115-121
Treatment with ginsenosides, the major active ingredients of Panax ginseng, produces a variety of physiological effects on the central and peripheral nervous systems. Ginsenosides inhibit various types of ligand-gated ion channel but it is not clear whether they act from within or outside the cell since they are somewhat membrane-permeable. In the present study, we used the Xenopus oocyte gene expression system to determine from which side of the cell membrane the ginsenoside Rg3 (Rg3), and M4, a ginsenoside metabolite, act to regulate ligand-gated ion channel activity. Ligand-gated ion currents were measured using the two-electrode voltage clamp technique. Rg3 and M4 inhibited 5-HT3A and a3b4 nACh receptor-mediated ion currents when present outside of the cell but not when injected intracellularly. We also examined the effect of these agents on oocytes expressing the gustatory cGMP-gated ion channel, which is known to have a cGMP binding site on the intracellular side of the plasma membrane and is only activated by cytosolic cGMP. Rg3 inhibited cGMP-gated ion currents when applied extracellularly or to an outside-out patch clamp, but not when injected into the cytosol or when using an excised inside-out patch clamp. These results indicate that Rg3 and M4 regulate ligand-gated ion channel activity from the extracellular side. 相似文献