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51.
Phylogeography of Y-chromosome haplogroup I reveals distinct domains of prehistoric gene flow in europe 总被引:14,自引:2,他引:12 下载免费PDF全文
Rootsi S Magri C Kivisild T Benuzzi G Help H Bermisheva M Kutuev I Barać L Pericić M Balanovsky O Pshenichnov A Dion D Grobei M Zhivotovsky LA Battaglia V Achilli A Al-Zahery N Parik J King R Cinnioğlu C Khusnutdinova E Rudan P Balanovska E Scheffrahn W Simonescu M Brehm A Goncalves R Rosa A Moisan JP Chaventre A Ferak V Füredi S Oefner PJ Shen P Beckman L Mikerezi I Terzić R Primorac D Cambon-Thomsen A Krumina A Torroni A Underhill PA Santachiara-Benerecetti AS Villems R Semino O 《American journal of human genetics》2004,75(1):128-137
To investigate which aspects of contemporary human Y-chromosome variation in Europe are characteristic of primary colonization, late-glacial expansions from refuge areas, Neolithic dispersals, or more recent events of gene flow, we have analyzed, in detail, haplogroup I (Hg I), the only major clade of the Y phylogeny that is widespread over Europe but virtually absent elsewhere. The analysis of 1,104 Hg I Y chromosomes, which were identified in the survey of 7,574 males from 60 population samples, revealed several subclades with distinct geographic distributions. Subclade I1a accounts for most of Hg I in Scandinavia, with a rapidly decreasing frequency toward both the East European Plain and the Atlantic fringe, but microsatellite diversity reveals that France could be the source region of the early spread of both I1a and the less common I1c. Also, I1b*, which extends from the eastern Adriatic to eastern Europe and declines noticeably toward the southern Balkans and abruptly toward the periphery of northern Italy, probably diffused after the Last Glacial Maximum from a homeland in eastern Europe or the Balkans. In contrast, I1b2 most likely arose in southern France/Iberia. Similarly to the other subclades, it underwent a postglacial expansion and marked the human colonization of Sardinia ~9,000 years ago. 相似文献
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Oliviero G Amato J Borbone N Galeone A Petraccone L Varra M Piccialli G Mayol L 《Bioconjugate chemistry》2006,17(4):889-898
Guanine-rich DNA sequences are widely dispersed in the eukaryotic genome and are abundant in regions with relevant biological significance. They can form quadruplex structures stabilized by guanine quartets. These structures differ for number and strand polarity, loop composition, and conformation. We report here the syntheses and the structural studies of a set of interconnected d(TG(4)T) fragments which are tethered, with different orientations, to a tetra-end-linker in an attempt to force the formation of specific four-stranded DNA quadruplex structures. Two synthetic strategies have been used to obtain oligodeoxyribonucleotide (ODN) strands linked with their 3'- or 5'-ends to each of the four arms of the linker. The first approach allowed the synthesis of tetra-end-linked ODN (TEL-ODN) containing the four ODN strands with a parallel orientation, while the latter synthetic pathway led to the synthesis of TEL-ODNs each containing antiparallel ODN pairs. The influence of the linker at 3'- or 5'-ODN, on the quadruplex typology and stability, in the presence of sodium or potassium ions, has been investigated by circular dichroism (CD), CD thermal denaturation, (1)H NMR experiments at variable temperature, and molecular modeling. All synthesized TEL-ODNs formed parallel G-quadruplex structures. Particularly, the TEL-ODN containing all parallel ODN tracts formed very stable parallel G-quadruplex complexes, whereas the TEL-ODNs containing antiparallel ODN pairs led to relatively less stable parallel G-quadruplexes. The molecular modeling data suggested that the above antiparallel TEL-ODNs can adopt parallel G-quadruplex structures thanks to a considerable folding of the tetra-end-linker around the whole quadruplex scaffold. 相似文献
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Leulliot N Vicentini G Jordens J Quevillon-Cheruel S Schiltz M Barford D van Tilbeurgh H Goris J 《Molecular cell》2006,23(3):413-424
PTPA, an essential and specific activator of protein phosphatase 2A (PP2A), functions as a peptidyl prolyl isomerase (PPIase). We present here the crystal structures of human PTPA and of the two yeast orthologs (Ypa1 and Ypa2), revealing an all alpha-helical protein fold that is radically different from other PPIases. The protein is organized into two domains separated by a groove lined by highly conserved residues. To understand the molecular mechanism of PTPA activity, Ypa1 was cocrystallized with a proline-containing PPIase peptide substrate. In the complex, the peptide binds at the interface of a peptide-induced dimer interface. Conserved residues of the interdomain groove contribute to the peptide binding site and dimer interface. Structure-guided mutational studies showed that in vivo PTPA activity is influenced by mutations on the surface of the peptide binding pocket, the same mutations that also influenced the in vitro activation of PP2Ai and PPIase activity. 相似文献
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Palmirotta R De Marchis ML Ludovici G Leone B Savonarola A Ialongo C Spila A De Angelis F Ferroni P Della-Morte D Guadagni F 《The International journal of biological markers》2012,27(2):e90-e98
Multicenter studies and biobanking projects require blood transportation from the participating center to a central collection or diagnostic laboratory. The impact of time delays between venous blood collection and peripheral blood mononuclear cells (PBMC) isolation prior to RNA extraction may affect the quality and quantity of isolated nucleic acids for genomic applications. Thus, standard operating procedure (SOP) optimization for the treatment of biological samples before RNA extraction is crucial in a biological repository. In order to define SOPs for whole blood preservation prior to RNA extraction, we sought to determine whether different blood storage times (0, 3, 6, 10, 24, and 30 hours) prior to PBMCs isolation and storage at -80°C, could affect the quality and quantity of extracted RNA. After spectrophotometric quantification, the quality and integrity of RNA were assessed by agarose gel electrophoresis, RNA integrity number and real time-PCR (RT-PCR).?Across the different time points we did not observe significant differences within the first 24 hours of blood storage at room temperature, while a significant loss in RNA yield and integrity was detected between 24 and 30 hours. We conclude that time delays before PBMCs isolation prior to RNA extraction may have a significant impact on downstream molecular biological applications. 相似文献
58.
Anti-angiogenic therapy has recently been added to the panel of cancer therapeutics, but predictive biomarkers of response are still not available. In animal models, anti-angiogenic therapy causes tumor starvation by increasing hypoxia and impairing nutrients supply. It is thus conceivable that angiogenesis inhibition causes remarkable metabolic perturbations in tumors, although they remain largely uncharted. We review here recent acquisitions about metabolic effects of angiogenesis blockade in tumors and discuss the possibility that some metabolic features of tumor cells - i.e. their dependency from glucose as primary energy substrate - might affect tumor responses to anti-VEGF treatment. 相似文献
59.
Manuela Priolo Enrico Grosso Corrado Mammì Claudia Labate Valeria Giorgia Naretto Caterina Vacalebre Paola Caridi Carmelo Laganà 《Gene》2012
The Nuclear Factor I-X (NFIX) is a member of the nuclear factor I (NFI) family proteins, which are implicated as site-specific DNA-binding proteins and is deleted or mutated in a subset of patients with Sotos-like overgrowth syndrome and in patients with Marshall–Smith syndrome. We evaluated an additional patient with clinical features of Sotos-like syndrome by sequencing analysis of the NFIX gene and identified a 21 nucleotide in frame deletion predicting loss of 7 amino acids in the DNA-binding/dimerization domain of the NFIX protein. The deleted residues are all evolutionally conserved amino acids. The present report further confirms that mutations in DNA-binding/dimerization domain cause haploinsufficiency of the NFIX protein and strongly suggests that in individuals with Sotos-like features unrelated to NSD1 changes genetic testing of NFIX should be considered. 相似文献
60.
Triolo D Dina G Taveggia C Vaccari I Porrello E Rivellini C Domi T La Marca R Cerri F Bolino A Quattrini A Previtali SC 《Development (Cambridge, England)》2012,139(7):1359-1367
Myelination is a complex process that requires coordinated Schwann cell-axon interactions during development and regeneration. Positive and negative regulators of myelination have been recently described, and can belong either to Schwann cells or neurons. Vimentin is a fibrous component present in both Schwann cell and neuron cytoskeleton, the expression of which is timely and spatially regulated during development and regeneration. We now report that vimentin negatively regulates myelination, as loss of vimentin results in peripheral nerve hypermyelination, owing to increased myelin thickness in vivo, in transgenic mice and in vitro in a myelinating co-culture system. We also show that this is due to a neuron-autonomous increase in the levels of axonal neuregulin 1 (NRG1) type III. Accordingly, genetic reduction of NRG1 type III in vimentin-null mice rescues hypermyelination. Finally, we demonstrate that vimentin acts synergistically with TACE, a negative regulator of NRG1 type III activity, as shown by hypermyelination of double Vim/Tace heterozygous mice. Our results reveal a novel role for the intermediate filament vimentin in myelination, and indicate vimentin as a regulator of NRG1 type III function. 相似文献