全文获取类型
收费全文 | 254篇 |
免费 | 34篇 |
专业分类
288篇 |
出版年
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 1篇 |
2019年 | 6篇 |
2018年 | 7篇 |
2017年 | 4篇 |
2016年 | 10篇 |
2015年 | 17篇 |
2014年 | 28篇 |
2013年 | 25篇 |
2012年 | 27篇 |
2011年 | 29篇 |
2010年 | 13篇 |
2009年 | 11篇 |
2008年 | 17篇 |
2007年 | 12篇 |
2006年 | 19篇 |
2005年 | 12篇 |
2004年 | 14篇 |
2003年 | 9篇 |
2002年 | 10篇 |
2001年 | 2篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1996年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1984年 | 1篇 |
排序方式: 共有288条查询结果,搜索用时 15 毫秒
201.
Michele Ciavarella Michelina Coco Filomena Baorda Pietro Stanziale Massimiliano Chetta Luigi Bisceglia Pietro Palumbo Mario Bengala Paola Raiteri Margherita Silengo Camilla Caldarini Renato Facchini Roberto Lala Maria Luigia Cavaliere Davide De Brasi Barbara Pasini Leopoldo Zelante Vito Guarnieri Leonardo D'Agruma 《Gene》2013
Background
Hereditary multiple exostosis represents the most frequent bone tumor disease in humans. It consists of cartilage deformities affecting the juxta-ephyseal region of long bones. Usually benign, exostosis could degenerate in malignant chondrosarcoma form in less than 5% of the cases. Being caused by mutations in the predicted tumor suppressor genes, EXT1 (chr 8q23-q24) and EXT2 (chr 11p11-p12) genes, HMEs are usually inherited with an autosomal dominant pattern, although “de novo” cases are not infrequent.Aim
Here we present our genetic diagnostic report on the largest Southern Italy cohort of HME patients consisting of 90 subjects recruited over the last 5 years.Results
Molecular screening performed by direct sequencing of both EXT1 and EXT2 genes, by MLPA and Array CGH analyses led to the identification of 66 mutations (56 different occurrences) and one large EXT2 deletion out of 90 patients (74.4%). The total of 21 mutations (20 different occurrences, 33.3%) and the EXT2 gene deletion were novel. In agreement with literature data, EXT1 gene mutations were scattered along all the protein sequence, while EXT2 lesions fell in the first part of the protein. Conservation, damaging prediction and 3-D modeling, in-silico, analyses, performed on three novel missense variants, confirmed that at least in two cases the novel aminoacidic changes could alter the structure stability causing a strong protein misfolding.Conclusions
Here we present 20 novel EXT1/EXT2 mutations and one large EXT2 deletion identified in the largest Southern Italy cohort of patients affected by hereditary multiple exostosis. 相似文献202.
203.
Competitive translation efficiency at the picornavirus type 1 internal ribosome entry site facilitated by viral cis and trans factors 下载免费PDF全文
Enteroviruses (EVs) overcome their host cells by usurping the translation machinery to benefit viral gene expression. This is accomplished through alternative translation initiation in a cap-independent manner at the viral internal ribosomal entry site (IRES). We have investigated the role of cis- and trans-acting viral factors in EV IRES translation in living cells. We observed that considerable portions of the viral genome, including the 5'-proximal open reading frame and the 3' untranslated region, contribute to stimulation of IRES-mediated translation. With the IRES in proper context, translation via internal initiation in uninfected cells is as efficient as at capped messages with short, unstructured 5' untranslated regions. IRES function is enhanced in cells infected with the EV coxsackievirus B3, but the related poliovirus has no significant stimulatory activity. This differential is due to the inherent properties of their 2A protease and is not coupled to 2A-mediated proteolytic degradation of the eukaryotic initiation factor 4G. Our results suggest that the efficiency of alternative translation initiation at EV IRESs depends on a properly configured template rather than on targeted alterations of the host cell translation machinery. 相似文献
204.
Frischknecht R Seidenbecher CI 《The international journal of biochemistry & cell biology》2012,44(7):1051-1054
Brevican is a neural proteoglycan implicated in a multitude of physiological and pathophysiological plasticity processes in the brain. It localizes to neuronal surfaces and contributes to the formation of specific types of extracellular matrix like the perineuronal nets or the perisynaptic or axon initial segment-based matrix in mature neuronal tissue. Via a variable degree of chondroitin sulfate attachment, limited proteolytic cleavage by matrix metalloproteinases, differential splicing and Ca(2+)-dependent binding to interaction partners it acts as a regulator in synaptic plasticity, glioma invasion, post-lesion plasticity or Alzheimer's disease. This review briefly summarizes its gene and protein structure, biochemical interactions and neurobiological functions. 相似文献
205.
Epstein-Barr Virus-Induced Expression of a Novel Human Vault RNA 总被引:1,自引:0,他引:1
Constanze Nandy Jan Mrázek Heribert Stoiber Alexander Hüttenhofer 《Journal of molecular biology》2009,388(4):776-216
Non-protein-coding RNAs (ncRNAs) have recently emerged on the scene of genomic research as prominent players in the regulation of gene expression. Many functionally characterized ncRNAs have been shown to be differentially expressed in various organisms during specific environmental or developmental conditions, thus establishing regulatory networks crucial for shaping cellular life. Here, we show that the expression of vault RNAs (vtRNAs) is specifically up-regulated in human lymphocytes upon infection by γ-herpesviruses, such as the Epstein-Barr virus and Kaposi's sarcoma virus. vtRNAs are ncRNAs that are integral to the vault complex, a gigantic (13 MDa) hollow ribonucleoprotein particle with a thus far elusive biological role. Stimulation of vtRNA expression by the Epstein-Barr virus was evident for all three canonical vtRNAs (hvg1-hvg3) and also for a novel ncRNA candidate, initially termed CBL-3. This ncRNA shares clear primary- and secondary-structure similarities with the three known vtRNAs. Importantly, CBL-3 co-sediments with intact vault particles in density gradients of various human cell lines, thus strongly indicating this ncRNA as a novel, fourth vault-complex-associated RNA. 相似文献
206.
The identification of expression variants is a challenge in HLA diagnostics. We here describe the identification of the novel
allele HLA-B*3565Q. The serological HLA class I type, as determined by a lymphocytotoxicity test, was A11,24; B38; Bw4; Cw−;
whereas PCR-sequence-specific primers resulted in A*11,*24, B*35,*38; Cw*12, thus suggesting the presence of a nonexpressed
B*35 allele. To clarify the lack of serological HLA-B35 reactivity, exons 2 and 3 were sequenced following haplotype-specific
amplification. At position 564 from the beginning of the coding region (exon 3), a transversion (C→G) was observed, which,
at the amino acid level, results in a substitution from cysteine to tryptophane at position 164 of the mature polypeptide.
Because this position is essential for the formation of a disulfide bond linking the cysteine residues at positions 101 and
164, which is strongly conserved in functional class I molecules of vertebrates, the disruption of this bond is very likely
to be the reason for the lack of serological detectability. We later found the same novel allele in a second unrelated individual,
of whom we were able to establish a lymphoblastoid cell line (B-LCL). Serological testing of this B-LCL indicated a very low
aberrant expression of HLA-B*3565Q, which cannot be expected to be detected by standard serology techniques.
Holger-Andreas Elsner and Peter A. Horn contributed equally to this work.
The nucleotide sequence data reported in this paper have been published in the European Molecular Biology Laboratory, GenBank,
and DNA Data Bank of Japan Nucleotide Sequence Database under the accession numbers AJ278746, AJ278747, and AJ879892. The
name B*3565Q was officially assigned by the WHO Nomenclature Committee in December 2005. This follows the agreed policy that,
subject to the conditions stated in the most recent Nomenclature Report (Marsh et al. 2005), names will be assigned to new sequences as they are identified. Lists of such new names will be published in the following
WHO Nomenclature Report. 相似文献
207.
208.
209.
Bj?rn Lamprecht Constanze Bonifer Stephan Mathas 《Cell cycle (Georgetown, Tex.)》2010,9(21):4276-4281
Recent data demonstrated that the raberrant activity of endogenous repetitive elements of the DNA in humans can drive the expression of proto-oncogenes. This article summarizes these results and gives an outlook on the impact of these findings on the pathogenesis and therapy of human cancer.Key words: LTR, Hodgkin lymphoma, CSF-1 receptor, epigenetic reprogramming, DNA methylation 相似文献
210.
Benz PM Blume C Moebius J Oschatz C Schuh K Sickmann A Walter U Feller SM Renné T 《The Journal of cell biology》2008,180(1):205-219
Directed cortical actin assembly is the driving force for intercellular adhesion. Regulated by phosphorylation, vasodilator-stimulated phosphoprotein (VASP) participates in actin fiber formation. We screened for endothelial proteins, which bind to VASP, dependent on its phosphorylation status. Differential proteomics identified αII-spectrin as such a VASP-interacting protein. αII-Spectrin binds to the VASP triple GP5-motif via its SH3 domain. cAMP-dependent protein kinase–mediated VASP phosphorylation at Ser157 inhibits αII-spectrin–VASP binding. VASP is dephosphorylated upon formation of cell–cell contacts and in confluent, but not in sparse cells, αII-spectrin colocalizes with nonphosphorylated VASP at cell–cell junctions. Ectopic expression of the αII-spectrin SH3 domain at cell–cell contacts translocates VASP, initiates cortical actin cytoskeleton formation, stabilizes cell–cell contacts, and decreases endothelial permeability. Conversely, the permeability of VASP-deficient endothelial cells (ECs) and microvessels of VASP-null mice increases. Reconstitution of VASP-deficient ECs rescues barrier function, whereas αII-spectrin binding-deficient VASP mutants fail to restore elevated permeability. We propose that αII-spectrin–VASP complexes regulate cortical actin cytoskeleton assembly with implications for vascular permeability. 相似文献