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51.
Single-electron transistor of a single organic molecule with access to several redox states 总被引:1,自引:0,他引:1
Kubatkin S Danilov A Hjort M Cornil J Brédas JL Stuhr-Hansen N Hedegård P Bjørnholm T 《Nature》2003,425(6959):698-701
A combination of classical Coulomb charging, electronic level spacings, spin, and vibrational modes determines the single-electron transfer reactions through nanoscale systems connected to external electrodes by tunnelling barriers. Coulomb charging effects have been shown to dominate such transport in semiconductor quantum dots, metallic and semiconducting nanoparticles, carbon nanotubes, and single molecules. Recently, transport has been shown to be also influenced by spin--through the Kondo effect--for both nanotubes and single molecules, as well as by vibrational fine structure. Here we describe a single-electron transistor where the electronic levels of a single pi-conjugated molecule in several distinct charged states control the transport properties. The molecular electronic levels extracted from the single-electron-transistor measurements are strongly perturbed compared to those of the molecule in solution, leading to a very significant reduction of the gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital. We suggest, and verify by simple model calculations, that this surprising effect could be caused by image charges generated in the source and drain electrodes resulting in a strong localization of the charges on the molecule. 相似文献
52.
Seandel M James D Shmelkov SV Falciatori I Kim J Chavala S Scherr DS Zhang F Torres R Gale NW Yancopoulos GD Murphy A Valenzuela DM Hobbs RM Pandolfi PP Rafii S 《Nature》2007,449(7160):346-350
Adult mammalian testis is a source of pluripotent stem cells. However, the lack of specific surface markers has hampered identification and tracking of the unrecognized subset of germ cells that gives rise to multipotent cells. Although embryonic-like cells can be derived from adult testis cultures after only several weeks in vitro, it is not known whether adult self-renewing spermatogonia in long-term culture can generate such stem cells as well. Here, we show that highly proliferative adult spermatogonial progenitor cells (SPCs) can be efficiently obtained by cultivation on mitotically inactivated testicular feeders containing CD34+ stromal cells. SPCs exhibit testicular repopulating activity in vivo and maintain the ability in long-term culture to give rise to multipotent adult spermatogonial-derived stem cells (MASCs). Furthermore, both SPCs and MASCs express GPR125, an orphan adhesion-type G-protein-coupled receptor. In knock-in mice bearing a GPR125-beta-galactosidase (LacZ) fusion protein under control of the native Gpr125 promoter (GPR125-LacZ), expression in the testis was detected exclusively in spermatogonia and not in differentiated germ cells. Primary GPR125-LacZ SPC lines retained GPR125 expression, underwent clonal expansion, maintained the phenotype of germline stem cells, and reconstituted spermatogenesis in busulphan-treated mice. Long-term cultures of GPR125+ SPCs (GSPCs) also converted into GPR125+ MASC colonies. GPR125+ MASCs generated derivatives of the three germ layers and contributed to chimaeric embryos, with concomitant downregulation of GPR125 during differentiation into GPR125- cells. MASCs also differentiated into contractile cardiac tissue in vitro and formed functional blood vessels in vivo. Molecular bookmarking by GPR125 in the adult mouse and, ultimately, in the human testis could enrich for a population of SPCs for derivation of GPR125+ MASCs, which may be employed for genetic manipulation, tissue regeneration and revascularization of ischaemic organs. 相似文献
53.
Edwards AM Phillips RA Watkins NW Freeman MP Murphy EJ Afanasyev V Buldyrev SV da Luz MG Raposo EP Stanley HE Viswanathan GM 《Nature》2007,449(7165):1044-1048
The study of animal foraging behaviour is of practical ecological importance, and exemplifies the wider scientific problem of optimizing search strategies. Lévy flights are random walks, the step lengths of which come from probability distributions with heavy power-law tails, such that clusters of short steps are connected by rare long steps. Lévy flights display fractal properties, have no typical scale, and occur in physical and chemical systems. An attempt to demonstrate their existence in a natural biological system presented evidence that wandering albatrosses perform Lévy flights when searching for prey on the ocean surface. This well known finding was followed by similar inferences about the search strategies of deer and bumblebees. These pioneering studies have triggered much theoretical work in physics (for example, refs 11, 12), as well as empirical ecological analyses regarding reindeer, microzooplankton, grey seals, spider monkeys and fishing boats. Here we analyse a new, high-resolution data set of wandering albatross flights, and find no evidence for Lévy flight behaviour. Instead we find that flight times are gamma distributed, with an exponential decay for the longest flights. We re-analyse the original albatross data using additional information, and conclude that the extremely long flights, essential for demonstrating Lévy flight behaviour, were spurious. Furthermore, we propose a widely applicable method to test for power-law distributions using likelihood and Akaike weights. We apply this to the four original deer and bumblebee data sets, finding that none exhibits evidence of Lévy flights, and that the original graphical approach is insufficient. Such a graphical approach has been adopted to conclude Lévy flight movement for other organisms, and to propose Lévy flight analysis as a potential real-time ecosystem monitoring tool. Our results question the strength of the empirical evidence for biological Lévy flights. 相似文献
54.
Scheper GC van der Klok T van Andel RJ van Berkel CG Sissler M Smet J Muravina TI Serkov SV Uziel G Bugiani M Schiffmann R Krägeloh-Mann I Smeitink JA Florentz C Van Coster R Pronk JC van der Knaap MS 《Nature genetics》2007,39(4):534-539
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) has recently been defined based on a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. LBSL is an autosomal recessive disease, most often manifesting in early childhood. Affected individuals develop slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline. We performed linkage mapping with microsatellite markers in LBSL families and found a candidate region on chromosome 1, which we narrowed by means of shared haplotypes. Sequencing of genes in this candidate region uncovered mutations in DARS2, which encodes mitochondrial aspartyl-tRNA synthetase, in affected individuals from all 30 families. Enzyme activities of mutant proteins were decreased. We were surprised to find that activities of mitochondrial complexes from fibroblasts and lymphoblasts derived from affected individuals were normal, as determined by different assays. 相似文献
55.
Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma 总被引:2,自引:0,他引:2
Nikolaev SI Rimoldi D Iseli C Valsesia A Robyr D Gehrig C Harshman K Guipponi M Bukach O Zoete V Michielin O Muehlethaler K Speiser D Beckmann JS Xenarios I Halazonetis TD Jongeneel CV Stevenson BJ Antonarakis SE 《Nature genetics》2012,44(2):133-139
We performed exome sequencing to detect somatic mutations in protein-coding regions in seven melanoma cell lines and donor-matched germline cells. All melanoma samples had high numbers of somatic mutations, which showed the hallmark of UV-induced DNA repair. Such a hallmark was absent in tumor sample-specific mutations in two metastases derived from the same individual. Two melanomas with non-canonical BRAF mutations harbored gain-of-function MAP2K1 and MAP2K2 (MEK1 and MEK2, respectively) mutations, resulting in constitutive ERK phosphorylation and higher resistance to MEK inhibitors. Screening a larger cohort of individuals with melanoma revealed the presence of recurring somatic MAP2K1 and MAP2K2 mutations, which occurred at an overall frequency of 8%. Furthermore, missense and nonsense somatic mutations were frequently found in three candidate melanoma genes, FAT4, LRP1B and DSC1. 相似文献
56.
57.
Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. 总被引:28,自引:0,他引:28
Sergey Kalachikov Oleg Evgrafov Barbara Ross Melodie Winawer Christie Barker-Cummings Filippo Martinelli Boneschi Chang Choi Pavel Morozov Kamna Das Elita Teplitskaya Andrew Yu Eftihia Cayanis Graciela Penchaszadeh Andreas H Kottmann Timothy A Pedley W Allen Hauser Ruth Ottman T Conrad Gilliam 《Nature genetics》2002,30(3):335-341
The epilepsies are a common, clinically heterogeneous group of disorders defined by recurrent unprovoked seizures. Here we describe identification of the causative gene in autosomal-dominant partial epilepsy with auditory features (ADPEAF, MIM 600512), a rare form of idiopathic lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. We constructed a complete, 4.2-Mb physical map across the genetically implicated disease-gene region, identified 28 putative genes (Fig. 1) and resequenced all or part of 21 genes before identifying presumptive mutations in one copy of the leucine-rich, glioma-inactivated 1 gene (LGI1) in each of five families with ADPEAF. Previous studies have indicated that loss of both copies of LGI1 promotes glial tumor progression. We show that the expression pattern of mouse Lgi1 is predominantly neuronal and is consistent with the anatomic regions involved in temporal lobe epilepsy. Discovery of LGI1 as a cause of ADPEAF suggests new avenues for research on pathogenic mechanisms of idiopathic epilepsies. 相似文献
58.
VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche 总被引:4,自引:0,他引:4
Kaplan RN Riba RD Zacharoulis S Bramley AH Vincent L Costa C MacDonald DD Jin DK Shido K Kerns SA Zhu Z Hicklin D Wu Y Port JL Altorki N Port ER Ruggero D Shmelkov SV Jensen KK Rafii S Lyden D 《Nature》2005,438(7069):820-827
The cellular and molecular mechanisms by which a tumour cell undergoes metastasis to a predetermined location are largely unknown. Here we demonstrate that bone marrow-derived haematopoietic progenitor cells that express vascular endothelial growth factor receptor 1 (VEGFR1; also known as Flt1) home to tumour-specific pre-metastatic sites and form cellular clusters before the arrival of tumour cells. Preventing VEGFR1 function using antibodies or by the removal of VEGFR1(+) cells from the bone marrow of wild-type mice abrogates the formation of these pre-metastatic clusters and prevents tumour metastasis, whereas reconstitution with selected Id3 (inhibitor of differentiation 3)-competent VEGFR1+ cells establishes cluster formation and tumour metastasis in Id3 knockout mice. We also show that VEGFR1+ cells express VLA-4 (also known as integrin alpha4beta1), and that tumour-specific growth factors upregulate fibronectin--a VLA-4 ligand--in resident fibroblasts, providing a permissive niche for incoming tumour cells. Conditioned media obtained from distinct tumour types with unique patterns of metastatic spread redirected fibronectin expression and cluster formation, thereby transforming the metastatic profile. These findings demonstrate a requirement for VEGFR1+ haematopoietic progenitors in the regulation of metastasis, and suggest that expression patterns of fibronectin and VEGFR1+VLA-4+ clusters dictate organ-specific tumour spread. 相似文献
59.
Alencar AM Arold SP Buldyrev SV Majumdar A Stamenović D Stanley HE Suki B 《Nature》2002,417(6891):809-811
In lung diseases such as asthma, expiratory flow becomes limited, airways can collapse and the vital exchange of gases is compromised. Here we model the inflation of collapsed regions of the lung during inspiration in terms of avalanches propagating through a bifurcating network of airways, and find that the accompanying cascade of dynamic pressure instabilities -- avalanche 'shocks' -- manifests as negative elastic resistance of the lung. Our analysis of this apparent thermodynamic paradox provides a better understanding of aeration in the deep regions of the lung, which may find application in medical conditions in which gas exchange is impaired. 相似文献
60.