全文获取类型
收费全文 | 290篇 |
免费 | 35篇 |
国内免费 | 1篇 |
出版年
2022年 | 2篇 |
2021年 | 4篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 12篇 |
2014年 | 17篇 |
2013年 | 26篇 |
2012年 | 26篇 |
2011年 | 26篇 |
2010年 | 11篇 |
2009年 | 20篇 |
2008年 | 14篇 |
2007年 | 20篇 |
2006年 | 20篇 |
2005年 | 6篇 |
2004年 | 14篇 |
2003年 | 15篇 |
2002年 | 9篇 |
2001年 | 10篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 12篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1991年 | 1篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有326条查询结果,搜索用时 78 毫秒
271.
The phytochrome gene family in grasses (Poaceae): a phylogeny and evidence that grasses have a subset of the loci found in dicot angiosperms 总被引:13,自引:2,他引:11
The phytochrome nuclear gene family encodes photoreceptor proteins that
mediate developmental responses to red and far red light throughout the
life of the plant. From studies of the dicot flowering plant Arabidopsis,
the family has been modeled as comprising five loci, PHYA- PHYE. However,
it has been shown recently that the Arabidopsis model may not completely
represent some flowering plant groups because additional PHY loci related
to PHYA and PHYB of Arabidopsis apparently have evolved independently
several times in dicots, and monocot flowering plants may lack orthologs of
PHYD and PHYE of Arabidopsis. Nonetheless, the phytochrome nucleotide data
were informative in a study of organismal evolution because the loci occur
as single copy sequences and appear to be evolving independently. We have
continued our investigation of the phytochrome gene family in flowering
plants by sampling extensively in the grass family. The phytochrome nuclear
DNA data were cladistically analyzed to address the following questions:
(1) Are the data consistent with a pattern of differential distribution of
phytochrome genes among monocots and higher dicots, with homologs of PHYA,
B, C, D, and E present in higher dicots, but of just PHYA, B, and C in
monocots, and (2) what phylogenetic pattern within Poaceae do they reveal?
Results of these analyses, and of Southern blot experiments, are consistent
with the observation that the phytochrome gene family in grasses comprises
the same subset of loci detected in other monocots. Furthermore, for
studies of organismal phylogeny in the grass family, the data are shown to
provide significant support for relationships that are just weakly resolved
by other data sets.
相似文献
272.
Melanosomes are tissue-specific lysosome-related organelles of pigment cells in which melanins are synthesized and stored. Analyses of the trafficking and fate of melanosomal components are beginning to reveal how melanosomes are formed through novel pathways from early endosomal intermediates. These studies unveil generalized structural and functional modifications of the endosomal system in specialized cells, and provide unexpected insights into the biogenesis of multivesicular bodies and how compartmentalization regulates protein refolding. Moreover, genetic disorders that affect the biogenesis of melanosomes and other lysosome-related organelles have shed light onto the molecular machinery that controls specialized endosomal sorting events. 相似文献
273.
Braun V Deschamps C Raposo G Benaroch P Benmerah A Chavrier P Niedergang F 《Molecular biology of the cell》2007,18(12):4921-4931
Phagocytosis, the mechanism of ingestion of large material and microorganisms, relies on actin polymerization and on the focal delivery of intracellular endocytic compartments. The molecular mechanisms involved in the formation and delivery of the endocytic vesicles that are recruited at sites of phagocytosis are not well characterized. Here we show that adaptor protein (AP)-1 but not AP-2 clathrin adaptor complexes are recruited early below the sites of particle attachment and are required for efficient receptor-mediated phagocytosis in murine macrophages. Clathrin, however, is not recruited with the AP complexes. We further show that the recruitment of AP-1-positive structures at sites of phagocytosis is regulated by the GTP-binding protein ARF1 but is not sensitive to brefeldin A. Furthermore, AP-1 depletion leads to increased surface levels of TNF-alpha, a cargo known to traffic through the endosomes to the plasma membrane upon stimulation of the macrophages. Together, our results support a clathrin-independent role for AP complexes in endosomal dynamics in macrophages by retaining some cargo proteins, a process important for membrane remodeling during phagocytosis. 相似文献
274.
BLOC-1 is required for cargo-specific sorting from vacuolar early endosomes toward lysosome-related organelles 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Setty SR Tenza D Truschel ST Chou E Sviderskaya EV Theos AC Lamoreux ML Di Pietro SM Starcevic M Bennett DC Dell'Angelica EC Raposo G Marks MS 《Molecular biology of the cell》2007,18(3):768-780
Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by defects in the formation and function of lysosome-related organelles such as melanosomes. HPS in humans or mice is caused by mutations in any of 15 genes, five of which encode subunits of biogenesis of lysosome-related organelles complex (BLOC)-1, a protein complex with no known function. Here, we show that BLOC-1 functions in selective cargo exit from early endosomes toward melanosomes. BLOC-1-deficient melanocytes accumulate the melanosomal protein tyrosinase-related protein-1 (Tyrp1), but not other melanosomal proteins, in endosomal vacuoles and the cell surface due to failed biosynthetic transit from early endosomes to melanosomes and consequent increased endocytic flux. The defects are corrected by restoration of the missing BLOC-1 subunit. Melanocytes from HPS model mice lacking a different protein complex, BLOC-2, accumulate Tyrp1 in distinct downstream endosomal intermediates, suggesting that BLOC-1 and BLOC-2 act sequentially in the same pathway. By contrast, intracellular Tyrp1 is correctly targeted to melanosomes in melanocytes lacking another HPS-associated protein complex, adaptor protein (AP)-3. The results indicate that melanosome maturation requires at least two cargo transport pathways directly from early endosomes to melanosomes, one pathway mediated by AP-3 and one pathway mediated by BLOC-1 and BLOC-2, that are deficient in several forms of HPS. 相似文献
275.
PCR-Based Strategy To Detect and Identify Species of Phaeoacremonium Causing Grapevine Diseases
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Species of Phaeoacremonium (especially Phaeoacremonium aleophilum) are associated with two severe diseases in grapevines, Petri disease in young plants and Esca disease in adult plants. Phaeoacremonium species grow slowly on culture medium, and it is difficult to identify these species on the basis of morphological characteristics. Primers Pm1 and Pm2 were designed in the ribosomal DNA internal transcribed spacer (ITS) regions ITS1 and ITS2, respectively. They yielded a single amplicon of 415 bp for nine species of Phaeoacremonium that may occur in grapevines. A nested PCR (using general fungal primers ITS1F/ITS4 in the primary reaction) was developed to detect Phaeoacremonium directly in grapevine wood. Molecular detection was more sensitive than the traditional method of culturing in growth medium was. Identification of Phaeoacremonium species was achieved by digesting the PCR-amplified fragment with the restriction enzymes BssKI, EcoO109I, and HhaI. It was possible to distinguish these species by their restriction fragment length polymorphism patterns, except for Phaeoacremonium viticola and Phaeoacremonium angustius, which had 100% similarity in their ITS region sequences. A species-specific PCR amplification of the partial β-tubulin gene using the primer pair Pbr4_1/T1 and Pbr8/T1 was necessary to differentiate P. angustius from P. viticola, respectively. An easy and fast protocol was developed to detect and identify species of Phaeoacremonium in a few hours. Primers defined here can be used in a plant nursery sanitation program to produce plants free of Phaeoacremonium spp. Use of healthy grapevine plants in new plantations is the most effective measure to manage Petri disease. 相似文献
276.
V Tiziani E Reichenberger C L Buzzo S Niazi N Fukai M Stiller H Peters F M Salzano C M Raposo do Amaral B R Olsen 《American journal of human genetics》1999,65(1):158-166
Cherubism is an autosomal dominant disorder that may be related to tooth development and eruption. It is a disorder of age-related bone remodeling, mostly limited to the maxilla and the mandible, with loss of bone in the jaws and its replacement with large amounts of fibrous tissue. We have used a genomewide search with a three-generation family and have established linkage to chromosome 4p16. Three other families affected with cherubism were also genotyped and were mapped to the same locus. The combined LOD score is 4.21 at a recombination fraction of 0, and the locus spans an interval of approximately 22 cM. 相似文献
277.
Degradation of extracellular matrix by mouse trophoblast outgrowths: a model for implantation 总被引:7,自引:6,他引:1
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
During implantation the embryo attaches to the endometrial surface and trophoblast traverses the uterine epithelium, anchoring in the uterine connective tissue. To determine whether trophoblast can facilitate invasion of the uterus by degrading components of normal uterine extracellular matrix, mouse blastocysts were cultured on a radio-labeled extracellular matrix that contained glycoproteins, elastin, and collagen. The embryos attached to the matrix, and trophoblast spread over the surface. Starting on day 5 of culture there was a release of labeled peptides into the medium. The radioactive peptides released from the matrix by the embryos had molecular weights ranging from more than 25,000 to more than 200. By day 7 there were areas where individual trophoblast cells had separated from one another, revealing the underlying substratum that was cleared of matrix. When trophoblast cells were lysed with NH(4)OH on day 8, it was apparent that the area underneath the trophoblast outgrowth had been cleared of matrix. Scanning electron microscopy and time-lapse cinemicrography confirmed that the digestion of matrix was highly localized, taking place only underneath the trophoblast, with no evidence of digestion of the matrix beyond the periphery of the trophoblast outgrowth. The sharp boundaries of degredation observed may be due to localized proteinase secretion by trophoblast, to membrane proteinases on the surface of trophoblast, or to endocytosis. Digestion of the matrix was not dependent on plasminogen, thus ruling out a role for plasminogen activator. Digestion was not inhibited by a variety of hormones and inhibitors, including progesterone, 17β-estradiol, leupeptin, EDTA, colchicine, NH(4)Cl, or ε-aminocaproic acid. This system of culturing embryos on extracellular matrix may be useful in determining the processes that regulate trophoblast migration and invasion into the maternal tissues during implantation.0 相似文献
278.
Partial 18S rRNA sequences of five chelicerate arthropods plus a
crustacean, myriapod, insect, chordate, echinoderm, annelid, and
platyhelminth were compared. The sequence data were used to infer phylogeny
by using a maximum-parsimony method, an evolutionary-distance method, and
the evolutionary-parsimony method. The phylogenetic inferences generated by
maximum-parsimony and distance methods support both monophyly of the
Arthropoda and monophyly of the Chelicerata within the Arthropoda. These
results are congruent with phylogenies based on rigorous cladistic analyses
of morphological characters. Results support the inclusion of the
Arthropoda within a spiralian or protostome coelomate clade that is the
sister group of a deuterostome clade, refuting the hypothesis that the
arthropods represent the "primitive" sister group of a protostome coelomate
clade. Bootstrap analyses and consideration of all trees within 1% of the
length of the most parsimonious tree suggest that relationships between the
nonchelicerate arthropods and relationships within the chelicerate clade
cannot be reliably inferred with the partial 18S rRNA sequence data. With
the evolutionary-parsimony method, support for monophyly of the Arthropoda
is found in the majority of the combinations analyzed if the coelomates are
used as "outgroups." Monophyly of the Chelicerata is supported in most
combinations assessed. Our analyses also indicate that the
evolutionary-parsimony method, like distance and parsimony, may be biased
by taxa with long branches. We suggest that a previous study's inference of
the Arthropoda as paraphyletic may be the result of (a) having two few
arthropod taxa available for analysis and (b) including long-branched taxa.
相似文献
279.
Valérie Brachet Gra?a Raposo Sebastian Amigorena Ira Mellman 《The Journal of cell biology》1997,137(1):51-65
Major histocompatibility complex class II molecules are synthesized as a nonameric complex consisting of three αβ dimers associated with a trimer of invariant (Ii) chains. After exiting the TGN, a targeting signal in the Ii chain cytoplasmic domain directs the complex to endosomes where Ii chain is proteolytically processed and removed, allowing class II molecules to bind antigenic peptides before reaching the cell surface. Ii chain dissociation and peptide binding are thought to occur in one or more postendosomal sites related either to endosomes (designated CIIV) or to lysosomes (designated MIIC). We now find that in addition to initially targeting αβ dimers to endosomes, Ii chain regulates the subsequent transport of class II molecules. Under normal conditions, murine A20 B cells transport all of their newly synthesized class II I-Ab αβ dimers to the plasma membrane with little if any reaching lysosomal compartments. Inhibition of Ii processing by the cysteine/serine protease inhibitor leupeptin, however, blocked transport to the cell surface and caused a dramatic but selective accumulation of I-Ab class II molecules in lysosomes. In leupeptin, I-Ab dimers formed stable complexes with a 10-kD NH2-terminal Ii chain fragment (Ii-p10), normally a transient intermediate in Ii chain processing. Upon removal of leupeptin, Ii-p10 was degraded and released, I-Ab dimers bound antigenic peptides, and the peptide-loaded dimers were transported slowly from lysosomes to the plasma membrane. Our results suggest that alterations in the rate or efficiency of Ii chain processing can alter the postendosomal sorting of class II molecules, resulting in the increased accumulation of αβ dimers in lysosome-like MIIC. Thus, simple differences in Ii chain processing may account for the highly variable amounts of class II found in lysosomal compartments of different cell types or at different developmental stages.The initiation of most immune responses requires antigen recognition by helper T lymphocytes. The antigen receptors on T cells can only recognize antigens as small peptides bound to major histocompatibility complex (MHC)1 class II molecules at the surface of antigen presenting cells (Cresswell, 1994; Germain, 1994). The complexes between class II molecules and antigenic peptides are formed intracellularly somewhere along the endocytic pathway (Germain, 1994; Wolf and Ploegh, 1995). This process requires the internalization of protein antigen and its delivery to a site suitable for the generation of antigenic peptides. In addition, the peptides must be generated within, or transferred to, a site to which newly synthesized MHC class II molecules are delivered and rendered competent for peptide binding (Davidson et al., 1991).Invariant (Ii) chain plays a central role in controlling the intracellular transport of MHC class II (Cresswell, 1996). In the ER, Ii chain is synthesized as a trimer that complexes with three αβ dimers of MHC class II (Roche et al., 1991). Its NH2-terminal cytoplasmic domain contains a wellknown targeting signal that directs class II–Ii chain complexes to endosomes after exit from the TGN (Bakke and Dobberstein, 1990; Lotteau et al., 1990; Neefjes et al., 1990; Odorizzi et al., 1994; Pieters et al., 1993). Once in endosomes, Ii chain is subjected to proteolysis by acid hydrolases (Roche and Cresswell, 1991). Degradation occurs in a stepwise fashion, resulting in the appearance of class II– bound NH2-terminal intermediates containing the Ii chain cytoplasmic domain, membrane anchor, and parts of its luminal domain (Newcomb and Cresswell, 1993). The intermediates accumulate in the presence of protease inhibitors that interfere with Ii chain processing such as the serinecysteine protease inhibitor leupeptin, treatment with which can also block the transport of at least some class II haplotypes to the cell surface (Amigorena et al., 1995; Blum and Cresswell, 1988; Neefjes and Ploegh, 1992). How leupeptin inhibits surface appearance is unknown.In human cells, Ii chain degradation intermediates include a 21–22-kD fragment (designated LIP [leupeptininducible peptide]) and a 10–12-kD fragment (designated SLIP [small leupeptin-inducible peptide]) (Blum and Cresswell, 1988; Maric et al., 1994). In murine cells, only a 10– 12-kD fragment has been identified (Ii-p10) (Amigorena et al., 1995). Ii-p10 remains as a trimer associated with three αβ dimers and blocks the binding of antigenic peptides (Amigorena et al., 1995; Morton et al., 1995). It is thus likely that Ii-p10 includes a luminal region of Ii chain (designated CLIP) known to occupy the peptide binding groove of αβ dimers. Cleavage of Ii-p10 by a leupeptinsensitive protease causes its dissociation from αβ dimers, while leaving CLIP in the peptide binding groove. The removal of CLIP is favored at acidic pH but is additionally catalyzed by a second MHC gene product, HLA-DM (Sloan et al., 1995; Denzin and Cresswell, 1995; Karlsson et al., 1994; Roche, 1995). In mutant cells lacking HLA-DM, there is defective loading of antigenic peptides and the appearance of CLIP-αβ dimers on the plasma membrane (Mellins et al., 1994; Riberdy et al., 1992).The precise site(s) where these events occur remains unclear. In A20 B cells, a specialized population of endosome-like vesicles designated CIIV (for class II vesicles) represents a site through which a majority of newly synthesized class II molecules pass en route to the cell surface and a place where antigenic peptides bind αβ dimers of the I-Ad haplotype (Amigorena et al., 1994, 1995; Barnes and Mitchell, 1995). CIIV are physically distinct from the bulk of endosomes and lysosomes and contain at least some HLA-DM (Pierre et al., 1996). Despite the fact that most of the αβ dimers reaching CIIV are newly synthesized, CIIV contain little or no intact Ii chain (Amigorena et al., 1995). Thus, Ii chain–αβ complexes first may be delivered to endosomes where Ii chain is cleaved before being delivered to CIIV. That peptide loading can occur in CIIV has been demonstrated by experiments showing that leupeptin causes CIIV to transiently accumulate Ii-p10– containing complexes, which can then bind peptide (Amigorena et al., 1995).In human Epstein-Barr virus–transformed B lymphoblasts, most class II molecules have been localized to structures collectively designated MIIC (for MHC class II compartment) (Peters et al., 1991; Tulp et al., 1994; West et al., 1994). MIICs differ from CIIVs in that the latter contain endosomal but not lysosomal markers, while MIICs have most or all of the features of lysosomes (Peters et al., 1991, 1995; Pierre et al., 1996). Interestingly, the distribution of class II between endosomal (CIIV) and lysosomal (MIIC) compartments varies widely among cell types. Since lysosomes are classically defined as terminal degradative organelles (Kornfeld and Mellman, 1989), such variations may reflect differences in the rates at which class II is turned over in different cell types. On the other hand, MIICs also contain the bulk of HLA-DM and can host the loading of antigenic peptides onto class II molecules (Sanderson et al., 1994). The extent to which these complexes escape degradation and reach the cell surface is unclear. Nor is it at all clear how different cell types regulate the intracellular distribution of class II molecules between early and late endocytic compartments.We now show that murine A20 cells expressing endogenous I-Ad and transfected I-Ab normally localize little class II in lysosomes. Selective lysosomal accumulation of I-Ab αβ dimers can be induced after leupeptin treatment. Interestingly, I-Ab dimers, but not I-Ad dimers, are induced by leupeptin to form stable complexes with Ii-p10. Upon removal of the inhibitor, the Ii-p10 was removed and class II molecules were slowly transported from lysosomes to the cell surface. Thus, the rate of dissociation of Ii chain intermediates can regulate whether newly synthesized class II molecules are transported to the plasma membrane or to lysosomes. 相似文献
280.
Comparison of the effects of concentration, pH and anion species on astringency and sourness of organic acids 总被引:4,自引:1,他引:3
The separate effects of concentration, pH and anion species on intensity of
sourness and astringency of organic acids were evaluated. Judges rated
sourness and astringency intensity of lactic, malic, tartaric and citric
acid solutions at three levels of constant pH varying in normality and at
three levels of constant concentration varying in pH. To assess the
comparative sourness and astringency of the organic acid anions of study,
binary acid solutions matched in pH and titratable acidity were also rated.
As pH was decreased in equinormal solutions, both sourness and astringency
increased significantly (P < 0.001). By contrast, as the normality of
the equi-pH solutions was increased, only sourness demonstrated significant
increases (P < 0.001) while astringency remained constant or decreased
slightly. At the lowest normality tested, all solutions were more
astringent than sour (P < 0.05). Although lactic acid was found to be
significantly more sour than citric acid (P < 0.05), no other sourness
or astringency differences among the organic acid anions were noted. This
study demonstrates for the first time that astringency elicited by acids is
a function of pH and not concentration or anion species, and confirms that
sourness is independently influenced by concentration, pH and anion species
of the acid.
相似文献