全文获取类型
收费全文 | 91篇 |
免费 | 11篇 |
专业分类
102篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 4篇 |
2014年 | 5篇 |
2013年 | 13篇 |
2012年 | 4篇 |
2011年 | 7篇 |
2010年 | 8篇 |
2009年 | 4篇 |
2008年 | 2篇 |
2007年 | 8篇 |
2006年 | 4篇 |
2005年 | 3篇 |
2004年 | 5篇 |
2003年 | 6篇 |
2002年 | 3篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1998年 | 1篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1979年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有102条查询结果,搜索用时 15 毫秒
51.
52.
Sabine Gorynia Todd C. Lorenz Giancarlo Costaguta Lydia Daboussi Duilio Cascio Gregory S. Payne 《Molecular biology of the cell》2012,23(22):4416-4429
Clathrin coat accessory proteins play key roles in transport mediated by clathrin-coated vesicles. Yeast Irc6p and the related mammalian p34 are putative clathrin accessory proteins that interact with clathrin adaptor complexes. We present evidence that Irc6p functions in clathrin-mediated traffic between the trans-Golgi network and endosomes, linking clathrin adaptor complex AP-1 and the Rab GTPase Ypt31p. The crystal structure of the Irc6p N-terminal domain revealed a G-protein fold most related to small G proteins of the Rab and Arf families. However, Irc6p lacks G-protein signature motifs and high-affinity GTP binding. Also, mutant Irc6p lacking candidate GTP-binding residues retained function. Mammalian p34 rescued growth defects in irc6∆ cells, indicating functional conservation, and modeling predicted a similar N-terminal fold in p34. Irc6p and p34 also contain functionally conserved C-terminal regions. Irc6p/p34-related proteins with the same two-part architecture are encoded in genomes of species as diverse as plants and humans. Together these results define Irc6p/p34 as a novel type of conserved clathrin accessory protein and founding members of a new G protein–like family. 相似文献
53.
Duilio Lausi 《Plant biosystems》2013,147(4):223-230
Abstract «Saxifraga berica» (Béguinot) D. A. Webb and «Asplenium lepidum» Presl on the «Colli Berici». – We have identified a new association in the small caverns of the calcareous rocks in the hills of the north-eastern zone of the «Colli Berici», rising from the Italian plain near Vicenza. We have adopted for this association the name: ADIANTO-SAXIFRAGETUM BERICAE. This phytocoenose is characterized by the endemic «Saxifraga berica». We have found new stations of this remarkable plant and reported some features of this species to complete the diagnosis of D. A. Webb. In two station of this association we have found also the rare «Asplenium lepidum», new for this region. 相似文献
54.
A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis 总被引:13,自引:0,他引:13 下载免费PDF全文
Nishimura AL Mitne-Neto M Silva HC Richieri-Costa A Middleton S Cascio D Kok F Oliveira JR Gillingwater T Webb J Skehel P Zatz M 《American journal of human genetics》2004,75(5):822-831
Motor neuron diseases (MNDs) are a group of neurodegenerative disorders with involvement of upper and/or lower motor neurons, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), progressive bulbar palsy, and primary lateral sclerosis. Recently, we have mapped a new locus for an atypical form of ALS/MND (atypical amyotrophic lateral sclerosis [ALS8]) at 20q13.3 in a large white Brazilian family. Here, we report the finding of a novel missense mutation in the vesicle-associated membrane protein/synaptobrevin-associated membrane protein B (VAPB) gene in patients from this family. Subsequently, the same mutation was identified in patients from six additional kindreds but with different clinical courses, such as ALS8, late-onset SMA, and typical severe ALS with rapid progression. Although it was not possible to link all these families, haplotype analysis suggests a founder effect. Members of the vesicle-associated proteins are intracellular membrane proteins that can associate with microtubules and that have been shown to have a function in membrane transport. These data suggest that clinically variable MNDs may be caused by a dysfunction in intracellular membrane trafficking. 相似文献
55.
Mark A. Arbing Sum Chan Liam Harris Emmeline Kuo Tina T. Zhou Christine J. Ahn Lin Nguyen Qixin He Jamie Lu Phuong T. Menchavez Annie Shin Thomas Holton Michael R. Sawaya Duilio Cascio David Eisenberg 《PloS one》2013,8(11)
The expression of heteroligomeric protein complexes for structural studies often requires a special coexpression strategy. The reason is that the solubility and proper folding of each subunit of the complex requires physical association with other subunits of the complex. The genomes of pathogenic mycobacteria encode many small protein complexes, implicated in bacterial fitness and pathogenicity, whose characterization may be further complicated by insolubility upon expression in Escherichia coli, the most common heterologous protein expression host. As protein fusions have been shown to dramatically affect the solubility of the proteins to which they are fused, we evaluated the ability of maltose binding protein fusions to produce mycobacterial Esx protein complexes. A single plasmid expression strategy using an N-terminal maltose binding protein fusion to the CFP-10 homolog proved effective in producing soluble Esx protein complexes, as determined by a small-scale expression and affinity purification screen, and coupled with intracellular proteolytic cleavage of the maltose binding protein moiety produced protein complexes of sufficient purity for structural studies. In comparison, the expression of complexes with hexahistidine affinity tags alone on the CFP-10 subunits failed to express in amounts sufficient for biochemical characterization. Using this strategy, six mycobacterial Esx complexes were expressed, purified to homogeneity, and subjected to crystallization screening and the crystal structures of the Mycobacterium abscessus EsxEF, M. smegmatis EsxGH, and M. tuberculosis EsxOP complexes were determined. Maltose binding protein fusions are thus an effective method for production of Esx complexes and this strategy may be applicable for production of other protein complexes. 相似文献
56.
Mahavir Singh Fernando A. Gonzales Duilio Cascio Nathanael Heckmann Guillaume Chanfreau Juli Feigon 《The Journal of biological chemistry》2009,284(3):1906-1916
H/ACA ribonucleoprotein particles are essential for ribosomal RNA and
telomerase RNA processing and metabolism. Shq1p has been identified as an
essential eukaryotic H/ACA small nucleolar (sno) ribonucleoparticle (snoRNP)
biogenesis and assembly factor. Shq1p is postulated to be involved in the
early biogenesis steps of H/ACA snoRNP complexes, and Shq1p depletion leads to
a specific decrease in H/ACA small nucleolar RNA levels and to defects in
ribosomal RNA processing. Shq1p contains two predicted domains as follows: an
N-terminal CS (named after CHORD-containing proteins and
SGT1) or HSP20-like domain, and a C-terminal region of high
sequence homology called the Shq1 domain. Here we report the crystal structure
and functional studies of the Saccharomyces cerevisiae Shq1p CS
domain. The structure consists of a compact anti-parallel β-sandwich fold
that is composed of two β-sheets containing four and three
β-strands, respectively, and a short α-helix. Deletion studies
showed that the CS domain is required for the essential functions of Shq1p.
Point mutations in residues Phe-6, Gln-10, and Lys-80 destabilize Shq1p in
vivo and induce a temperature-sensitive phenotype with depletion of H/ACA
small nucleolar RNAs and defects in rRNA processing. Although CS domains are
frequently found in co-chaperones of the Hsp90 molecular chaperone, no
interaction was detected between the Shq1p CS domain and yeast Hsp90 in
vitro. These results show that the CS domain is essential for Shq1p
function in H/ACA snoRNP biogenesis in vivo, possibly in an
Hsp90-independent manner.Modification of uridine to pseudouridine in ribosomal RNA and some
spliceosomal RNAs is catalyzed by highly specialized ribonucleoparticle
(RNP)3 complexes
called box H/ACA RNPs
(1-5).
Depending on their site of maturation and action H/ACA RNPs are classified
into two classes, small nucleolar RNPs (snoRNPs) and small Cajal body RNPs. In
Saccharomyces cerevisiae, H/ACA snoRNPs contain four proteins: Nhp2p
(L7ae in archaea (6) and Cbf5p,
also called dyskerin, in humans
(7)), Nop10p, Gar1p, and a
single small nucleolar RNA (snoRNA), specific to each snoRNP
(8-11).
Cbf5p provides the pseudouridylase activity to the complex, and the snoRNA
component provides the “guide RNA” for positioning the substrate
RNA for modification (8,
10,
12-15).
The 3′ end of human telomerase RNA (hTR) contains an H/ACA scaRNA domain
that binds the H/ACA proteins and is required for 3′ end processing,
accumulation, and localization of hTR to Cajal bodies
(16-19).
In archaea, the assembly of H/ACA snoRNP appears to proceed by assembly of the
protein components, followed by the incorporation of the H/ACA RNA
(8,
20-23).
In eukaryotes, the assembly and final maturation of the holoenzyme RNP are
more complicated, possibly because of subcellular compartmentalization, and
require accessory proteins
(22,
24). Two proteins specifically
found in eukaryotes, Naf1p and Shq1p, were initially identified in yeast as
factors involved in the assembly of H/ACA snoRNPs
(23-25).
Both Shq1p and Naf1p are essential proteins, and their depletion leads to the
loss of H/ACA snoRNAs (22,
24). Shq1p and Naf1p interact
with the H/ACA RNP components Cbf5p and Nhp2p as shown by high throughput
proteomic approaches and by directed protein interaction studies
(24,
26-28).
Both Naf1p and Gar1p contain a central domain that forms a six-stranded
β-barrel fold and interact competitively with Cbf5p using this
“core-Gar1” domain
(29).Although Shq1p was first identified in yeast
(24), orthologues have been
found in all eukaryotic genomes investigated, including human
(22). Shq1p is not associated
with the precursor or mature RNPs and is localized in the nucleoplasm
(24) rather than in the
nucleolus or Cajal bodies where mature H/ACA RNPs reside. It was therefore
proposed that Shq1p is involved in the early biogenesis steps of H/ACA
snoRNPs. However, Shq1p does not share any homology with either Naf1p or
Gar1p, and its mode of action remains unclear. Based on the Saccharomyces
Genome Data base annotations and domain predictions, Shq1p seems to be a
modular protein with two predicted domains in its sequence
(Fig. 1A). The
C-terminal half contains a region of high sequence homology with other Shq1
proteins called the Shq1 domain, but this region shows no identified folding
motif. The N-terminal region of the protein has a predicted CS (named after
CHORD-containing proteins and SGT1) or HSP20-like
domain, which is found in a number of co-chaperones for heat shock protein 90
(Hsp90)
(30-34),
and hence is presumed to be an Hsp90 (Hsp82p in yeast) binding domain. The CS,
HSP20-like, and p23-like domains belong to the HSP20 domain superfamily.Open in a separate windowFIGURE 1.Deletion analysis and stability of Shq1p truncated mutants.
A, domain organization of Shq1p and complementation of the
shq1Δ strain by the various truncation mutants.
Numbers refer to SHQ1 amino acid residues. Cells were grown
in plates containing 5-fluoroacetic acid to counterselect the wild-type
(wt) SHQ1 copy borne by the URA3-containing plasmid
and in the absence of methionine to express Shq1p, and cell growth was
assessed. B, example of growth assay used to generate the previous
figure. Shown is the growth of strains expressing the indicated deletions of
Shq1p on a plate containing 5-fluoroacetic acid to counterselect the wild-type
SHQ1 copy borne by the URA3-containing plasmid. C,
stability of truncated mutants. Cells containing the endogenous SHQ1 copy and
the indicated constructs were grown on liquid medium in the absence of
methionine. Proteins were expressed under the control of the Met25 promoter,
which is highly induced in the absence of Met. Numbers refer to SHQ1
amino acid residues. Shq1p proteins were detected by immunoblotting with
anti-GFP. Hexokinase (Hxk) was used as a loading control.We have determined the x-ray crystal structure of the CS domain of Shq1p
and investigated its importance for Shq1p function. The structure consists of
a β-sandwich immunoglobulin light chain fold
(35). Like other CS domains,
the CS domain of Shq1p is primarily composed of two β-sheets
(30,
31,
33,
36), but it has an additional
short helix at the C terminus. We show that the Shq1p CS domain is essential
for growth in S. cerevisiae and that the integrity of the CS domain
is required for the function of Shq1p in vivo. Based on the structure
and sequence conservation among Shq1 proteins, we investigated the effect of
three single point mutations, F6A, Q10A, and K80A, on Shq1p structure and
function. All three mutations destabilized the tertiary structure of the CS
domain, albeit to differing extents. Incorporation of these mutations in Shq1p
resulted in a temperature-sensitive growth phenotype, specific depletion of
H/ACA snoRNAs, and rRNA processing defects. NMR chemical shift mapping showed
no interaction between the Shq1p CS domain and Hsp82p, suggesting that the
Shq1p CS domain does not have a canonical role as an Hsp82p co-chaperone
protein. 相似文献
57.
Mizuki Aoki Jeffrey Vinokur Kento Motoyama Rino Ishikawa Michael Collazo Duilio Cascio Michael R. Sawaya Tomokazu Ito James U. Bowie Hisashi Hemmi 《The Journal of biological chemistry》2022,298(7)
Mevalonate 3,5-bisphosphate decarboxylase is involved in the recently discovered Thermoplasma-type mevalonate pathway. The enzyme catalyzes the elimination of the 3-phosphate group from mevalonate 3,5-bisphosphate as well as concomitant decarboxylation of the substrate. This entire reaction of the enzyme resembles the latter half-reactions of its homologs, diphosphomevalonate decarboxylase and phosphomevalonate decarboxylase, which also catalyze ATP-dependent phosphorylation of the 3-hydroxyl group of their substrates. However, the crystal structure of mevalonate 3,5-bisphosphate decarboxylase and the structural reasons of the difference between reactions catalyzed by the enzyme and its homologs are unknown. In this study, we determined the X-ray crystal structure of mevalonate 3,5-bisphosphate decarboxylase from Picrophilus torridus, a thermoacidophilic archaeon of the order Thermoplasmatales. Structural and mutational analysis demonstrated the importance of a conserved aspartate residue for enzyme activity. In addition, although crystallization was performed in the absence of substrate or ligands, residual electron density having the shape of a fatty acid was observed at a position overlapping the ATP-binding site of the homologous enzyme, diphosphomevalonate decarboxylase. This finding is in agreement with the expected evolutionary route from phosphomevalonate decarboxylase (ATP-dependent) to mevalonate 3,5-bisphosphate decarboxylase (ATP-independent) through the loss of kinase activity. We found that the binding of geranylgeranyl diphosphate, an intermediate of the archeal isoprenoid biosynthesis pathway, evoked significant activation of mevalonate 3,5-bisphosphate decarboxylase, and several mutations at the putative geranylgeranyl diphosphate–binding site impaired this activation, suggesting the physiological importance of ligand binding as well as a possible novel regulatory system employed by the Thermoplasma-type mevalonate pathway. 相似文献
58.
Lorena Saelices Lisa M. Johnson Wilson Y. Liang Michael R. Sawaya Duilio Cascio Piotr Ruchala Julian Whitelegge Lin Jiang Roland Riek David S. Eisenberg 《The Journal of biological chemistry》2015,290(48):28932-28943
The tetrameric thyroxine transport protein transthyretin (TTR) forms amyloid fibrils upon dissociation and monomer unfolding. The aggregation of transthyretin has been reported as the cause of the life-threatening transthyretin amyloidosis. The standard treatment of familial cases of TTR amyloidosis has been liver transplantation. Although aggregation-preventing strategies involving ligands are known, understanding the mechanism of TTR aggregation can lead to additional inhibition approaches. Several models of TTR amyloid fibrils have been proposed, but the segments that drive aggregation of the protein have remained unknown. Here we identify β-strands F and H as necessary for TTR aggregation. Based on the crystal structures of these segments, we designed two non-natural peptide inhibitors that block aggregation. This work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy. 相似文献
59.
Duilio Michele Potenza Germano Guerra Daniele Avanzato Valentina Poletto Sumedha Pareek Daniele Guido Angelo Gallanti Vittorio Rosti Luca Munaron Franco Tanzi Francesco Moccia 《Cell calcium》2014
Hydrogen sulphide (H2S) is a newly discovered gasotransmitter that regulates multiple steps in VEGF-induced angiogenesis. An increase in intracellular Ca2+ concentration ([Ca2+]i) is central to endothelial proliferation and may be triggered by both VEGF and H2S. Albeit VEGFR-2 might serve as H2S receptor, the mechanistic relationship between VEGF- and H2S-induced Ca2+ signals in endothelial cells is unclear. The present study aimed at assessing whether and how NaHS, a widely employed H2S donor, stimulates pro-angiogenic Ca2+ signals in Ea.hy926 cells, a suitable surrogate for mature endothelial cells, and human endothelial progenitor cells (EPCs). We found that NaHS induced a dose-dependent increase in [Ca2+]i in Ea.hy926 cells. NaHS-induced Ca2+ signals in Ea.hy926 cells did not require extracellular Ca2+ entry, while they were inhibited upon pharmacological blockade of the phospholipase C/inositol-1,4,5-trisphosphate (InsP3) signalling pathway. Moreover, the Ca2+ response to NaHS was prevented by genistein, but not by SU5416, which selectively inhibits VEGFR-2. However, VEGF-induced Ca2+ signals were suppressed by dl-propargylglycine (PAG), which blocks the H2S-producing enzyme, cystathionine γ-lyase. Consistent with these data, VEGF-induced proliferation and migration were inhibited by PAG in Ea.hy926 cells, albeit NaHS alone did not influence these processes. Conversely, NaHS elevated [Ca2+]i only in a modest fraction of circulating EPCs, whereas neither VEGF-induced Ca2+ oscillations nor VEGF-dependent proliferation were affected by PAG. Therefore, H2S-evoked elevation in [Ca2+]i is essential to trigger the pro-angiogenic Ca2+ response to VEGF in mature endothelial cells, but not in their immature progenitors. 相似文献
60.
Mark R. Fleissner Duilio Cascio Wayne L. Hubbell 《Protein science : a publication of the Protein Society》2009,18(5):893-908
A disulfide-linked nitroxide side chain (R1) used in site-directed spin labeling of proteins often exhibits an EPR spectrum characteristic of a weakly ordered z-axis anisotropic motion at topographically diverse surface sites, including those on helices, loops and edge strands of β-sheets. To elucidate the origin of this motion, the first crystal structures of R1 that display simple z-axis anisotropic motion at solvent-exposed helical sites (131 and 151) and a loop site (82) in T4 lysozyme have been determined. Structures of 131R1 and 151R1 determined at cryogenic or ambient temperature reveal an intraresidue Cα—H···Sδ interaction that immobilizes the disulfide group, consistent with a model in which the internal motions of R1 are dominated by rotations about the two terminal bonds (Columbus, Kálai, Jeko, Hideg, and Hubbell, Biochemistry 2001;40:3828–3846). Remarkably, the 131R1 side chain populates two rotamers equally, but the EPR spectrum reflects a single dominant dynamic population, showing that the two rotamers have similar internal motion determined by the common disulfide-backbone interaction. The anisotropic motion for loop residue 82R1 is also accounted for by a common disulfide-backbone interaction, showing that the interaction does not require a specific secondary structure. If the above observations prove to be general, then significant variations in order and rate for R1 at noninteracting solvent-exposed helical and loop sites can be assigned to backbone motion because the internal motion is essentially constant. 相似文献