全文获取类型
收费全文 | 118篇 |
免费 | 6篇 |
专业分类
124篇 |
出版年
2022年 | 1篇 |
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 6篇 |
2015年 | 11篇 |
2014年 | 5篇 |
2013年 | 3篇 |
2012年 | 8篇 |
2011年 | 3篇 |
2010年 | 6篇 |
2009年 | 4篇 |
2008年 | 9篇 |
2007年 | 4篇 |
2006年 | 6篇 |
2005年 | 8篇 |
2004年 | 4篇 |
2003年 | 2篇 |
2002年 | 6篇 |
2001年 | 2篇 |
2000年 | 6篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
排序方式: 共有124条查询结果,搜索用时 15 毫秒
101.
Sara S Roscioni Loes EM Kistemaker Mark H Menzen Carolina RS Elzinga Reinoud Gosens Andrew J Halayko Herman Meurs Martina Schmidt 《Respiratory research》2009,10(1):1-17
Background
Platelet-derived growth factor A (PDGF-A) signals solely through PDGF-Rα, and is required for fibroblast proliferation and transdifferentiation (fibroblast to myofibroblast conversion) during alveolar development, because pdgfa-null mice lack both myofibroblasts and alveoli. However, these PDGF-A-mediated mechanisms remain incompletely defined. At postnatal days 4 and 12 (P4 and P12), using mouse lung fibroblasts, we examined (a) how PDGF-Rα correlates with ki67 (proliferation marker) or alpha-smooth muscle actin (αSMA, myofibroblast marker) expression, and (b) whether PDGF-A directly affects αSMA or modifies stimulation by transforming growth factor beta (TGFβ).Methods
Using flow cytometry we examined PDGF-Rα, αSMA and Ki67 in mice which express green fluorescent protein (GFP) as a marker for PDGF-Rα expression. Using real-time RT-PCR we quantified αSMA mRNA in cultured Mlg neonatal mouse lung fibroblasts after treatment with PDGF-A, and/or TGFβ.Results
The intensity of GFP-fluorescence enabled us to distinguish three groups of fibroblasts which exhibited absent, lower, or higher levels of PDGF-Rα. At P4, more of the higher than lower PDGF-Rα + fibroblasts contained Ki67 (Ki67+), and Ki67+ fibroblasts predominated in the αSMA + but not the αSMA- population. By P12, Ki67+ fibroblasts comprised a minority in both the PDGF-Rα + and αSMA+ populations. At P4, most Ki67+ fibroblasts were PDGF-Rα + and αSMA- whereas at P12, most Ki67+ fibroblasts were PDGF-Rα- and αSMA-. More of the PDGF-Rα + than - fibroblasts contained αSMA at both P4 and P12. In the lung, proximate αSMA was more abundant around nuclei in cells expressing high than low levels of PDGF-Rα at both P4 and P12. Nuclear SMAD 2/3 declined from P4 to P12 in PDGF-Rα-, but not in PDGF-Rα + cells. In Mlg fibroblasts, αSMA mRNA increased after exposure to TGFβ, but declined after treatment with PDGF-A.Conclusion
During both septal eruption (P4) and elongation (P12), alveolar PDGF-Rα may enhance the propensity of fibroblasts to transdifferentiate rather than directly stimulate αSMA, which preferentially localizes to non-proliferating fibroblasts. In accordance, PDGF-Rα more dominantly influences fibroblast proliferation at P4 than at P12. In the lung, TGFβ may overshadow the antagonistic effects of PDGF-A/PDGF-Rα signaling, enhancing αSMA-abundance in PDGF-Rα-expressing fibroblasts. 相似文献102.
103.
L. G. Vasil'chenko V. V. Khromonygina O. V. Koroleva E. O. Landesman V. V. Gaponenko T. A. Kovaleva Yu. P. Kozlov M. L. Rabinovich 《Applied Biochemistry and Microbiology》2002,38(5):454-459
Asporogenic fungus Mycelia sterilia INBI 2-26 isolated from tropical soils with high residual dioxin content (as a result of Agent Orange defoliant treatment during the Vietnamese–American war) and capable of atrazine decomposition was treated to obtain protoplasts. This technique resulted in isolation of laccase-positive and laccase-negative clones. Atrazine consumption by liquid surface cultures of Mycelia sterilia INBI 2-26 was monitored by using enzyme immune assay and reversed-phase HPLC. Atrazine (20 g/ml) stimulated fungal growth. The laccase-positive clone consumed up to 80% of atrazine within four weeks. However, no correlation of atrazine consumption and laccase activity in the culture medium was observed. Moreover, the laccase-negative clone was also capable of consuming at least 60–70% of atrazine within three weeks. Surprisingly, in the corresponding control set (cultivation of laccase-negative clone without atrazine) an unidentified metabolite having a retention time and UV-spectrum similar to those of atrazine was also found. It was concluded that the presence of laccase was not a crucial factor in atrazine consumption by this fungus. 相似文献
104.
Conservation of alternative splicing and genomic organization of the myosin alkali light-chain (Mlc1) gene among Drosophila species 总被引:3,自引:0,他引:3
The Mlc1 gene of Drosophila melanogaster encodes two MLC1 isoforms via
developmentally regulated alternative pre-mRNA splicing. In larval muscle
and tubular and abdominal muscles of adults, all of the six exons are
included in the spliced mRNA, whereas, in the fibrillar indirect flight
muscle of adult, exon 5 is excluded from the mRNA. We show that this
tissue-specific pattern of alternative splicing of the Mlc1 pre-mRNA is
conserved in D. simulans, D. pseudoobscura, and D. virilis. Isolation and
sequencing of the Mlc1 genes from these three other Drosophila species have
revealed that the overall organization of the genes is identical and that
the genes have maintained a very high level of sequence identity within the
coding region. Pairwise amino acid identities are 94%-99%, and there are no
charge changes among the proteins. Total nucleotide divergence within the
coding region of the four genes supports the accepted genealogy of these
species, but the data indicate a significantly higher rate of amino acid
replacement in the branch leading to D. pseudoobscura. A comparison of
nucleotide substitutions in the coding portions of exon 5 and exon 6, which
encode the alternative carboxyl termini of the two MLC1 isoforms, suggests
that exon 5 is subject to greater evolutionary constraints than is exon 6.
In addition to the coding sequences, there is significant sequence
conservation within the 5' and 3' noncoding DNA and two of the introns,
including one that flanks exon 5. These regions are candidates for cis-
regulatory elements. Our results suggest that evolutionary constraints are
acting on both the coding and noncoding sequences of the Mlc1 gene to
maintain proper expression and function of the two MLC1 polypeptides.
相似文献
105.
Background
The YjgF/YER057c/UK114 family of proteins is widespread in nature, but has as yet no clearly defined biological role. Members of the family exist as homotrimers and are characterised by intersubunit clefts that are delineated by well-conserved residues; these sites are likely to be of functional significance, yet catalytic activity has never been detected for any member of this family. The gene encoding the TdcF protein of E. coli, a YjgF/YER057c/UK114 family member, resides in an operon that strongly suggests a role in the metabolism of 2-ketobutyrate for this protein. 相似文献106.
107.
Hyunbum Jang Sherwin J. Abraham Tanmay S. Chavan Ben Hitchinson Lyuba Khavrutskii Nadya I. Tarasova Ruth Nussinov Vadim Gaponenko 《The Journal of biological chemistry》2015,290(15):9465-9477
K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling. 相似文献
108.
Recognition and identification of protein folds is a prerequisite for high-throughput structural genomics. Here we demonstrate a simple protocol for covalent attachment of a short and more rigid metal-chelating tag, thiol-reactive EDTA, by chemical modification of the single cysteine residue in barnase(H102C). Conjugation of the metal-chelating tag provides the advantage of allowing a greater range of paramagnetic metal substitutions. Substitution of Yb(3+), Mn(2+), and Co(2+) permitted measurement of metal-amide proton distances, dipolar shifts, and residual dipolar couplings. Paramagnetic-derived restraints are advantageous in the NMR structure elucidation of large protein complexes and are shown sufficient for validation of homology-based fold predictions. 相似文献
109.
Molecular phylogenetic evidence that the phylum Haplosporidia has an alveolate ancestry 总被引:1,自引:0,他引:1
The phylogenetic position of the phylum Haplosporidia among other protists
was investigated with the complete 16S-like rRNA gene sequences from two
species in the phylum: Haplosporidium nelsoni, a parasite of oysters, and
Minchinia teredinis, a parasite of shipworms. Because the lack of obvious
morphological homologies with other protists hampered decisions regarding
taxonomic composition for sequence alignment and phylogenetic analysis, the
complete sequences for these two haplosporidians were directed as search
queries to the blast/ncbi.nlm.nih.gov electronic mail server. The results
of this heuristic similarity search provided a basis for constructing a
preliminary higher-taxonomic-level analysis comparing the haplosporidians
with species from the slime molds, fungi, algae, amoebae, ciliates,
dinoflagellates, and apicomplexans. Maximum parsimony yielded equivocal
results, whereas transversionally weighted parsimony suggested an affinity
with the alveolates (i.e., the ciliates, dinoflagellates, and
apicomplexans). Multiple alignment of the two haplosporidian sequences
against 17 taxa in a secondary analysis focusing on the alveolates and
subsequent parsimony analysis placed the phylum Haplosporidia as a
monophyletic group within the Alveolata and as a taxon of equal rank with
the other three alveolate phyla. The precise placement within the Alveolata
was sensitive to weighting.
相似文献
110.