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991.
María Jose Rebollo-Lopez Jo?l Lelièvre Daniel Alvarez-Gomez Julia Castro-Pichel Francisco Martínez-Jiménez George Papadatos Vinod Kumar Gonzalo Colmenarejo Grace Mugumbate Mark Hurle Vanessa Barroso Rob J. Young María Martinez-Hoyos Rubén González del Río Robert H. Bates Eva Maria Lopez-Roman Alfonso Mendoza-Losana James R. Brown Emilio Alvarez-Ruiz Marc A. Marti-Renom John P. Overington Nicholas Cammack Lluís Ballell David Barros-Aguire 《PloS one》2015,10(12)
As a follow up to the antimycobacterial screening exercise and the release of GSK´s first Tres Cantos Antimycobacterial Set (TCAMS-TB), this paper presents the results of a second antitubercular screening effort of two hundred and fifty thousand compounds recently added to the GSK collection. The compounds were further prioritized based on not only antitubercular potency but also on physicochemical characteristics. The 50 most attractive compounds were then progressed for evaluation in three different predictive computational biology algorithms based on structural similarity or GSK historical biological assay data in order to determine their possible mechanisms of action. This effort has resulted in the identification of novel compounds and their hypothesized targets that will hopefully fuel future TB drug discovery and target validation programs alike. 相似文献
992.
993.
Sankar P. Chaki Rola Barhoumi Gonzalo M. Rivera 《Molecular biology of the cell》2015,26(17):3047-3060
Multiple angiogenic cues modulate phosphotyrosine signaling to promote vasculogenesis and angiogenesis. Despite its functional and clinical importance, how vascular cells integrate phosphotyrosine-dependent signaling to elicit cytoskeletal changes required for endothelial morphogenesis remains poorly understood. The family of Nck adaptors couples phosphotyrosine signals with actin dynamics and therefore is well positioned to orchestrate cellular processes required in vascular formation and remodeling. Culture of endothelial cells in three-dimensional collagen matrices in the presence of VEGF stimulation was combined with molecular genetics, optical imaging, and biochemistry to show that Nck-dependent actin remodeling promotes endothelial cell elongation and proper organization of VE-cadherin intercellular junctions. Major morphogenetic defects caused by abrogation of Nck signaling included loss of endothelial apical-basal polarity and impaired lumenization. Time-lapse imaging using a Förster resonance energy transfer biosensor, immunostaining with phospho-specific antibodies, and GST pull-down assays showed that Nck determines spatiotemporal patterns of Cdc42/aPKC activation during endothelial morphogenesis. Our results demonstrate that Nck acts as an important hub integrating angiogenic cues with cytoskeletal changes that enable endothelial apical-basal polarization and lumen formation. These findings point to Nck as an emergent target for effective antiangiogenic therapy. 相似文献
994.
Manuel I. Osorio Matías A. Zúñiga Fernanda Mendoza Gonzalo A. Jaña Verónica A. Jiménez 《Proteins》2019,87(1):74-80
Glucansucrase GTF-SI from Streptococcus mutans is a multidomain enzyme that catalyzes the synthesis of glucan polymers. Domain V locates 100 Å from the catalytic site and is required for an optimal activity. Nevertheless, the mechanism governing its functional role remains elusive. In this work, homology modeling and molecular dynamics simulations were employed to examine the effect of domain V in the structure and glucan-binding ability of GTF-SI in full and truncated enzyme models. Our results showed that domain V increases the flexibility of the α4′-loop-α4″ motif near the catalytic site resulting in a higher surface for glucan association, and modulates the orientation of a growing oligosaccharide (N=8-23) in glucan-enzyme complexes towards engaging in favorable contacts throughout the protein, whereas in the truncated model the glucan protrudes randomly from domain B towards the solvent. These results are valuable to increase understanding about the functional role of domain V in GH70 glucansucrases. 相似文献
995.
We report the finding of terrestrial nemerteans of the family Acteonemertidae from the northern part of Spain. The specimens were studied using molecular data from the nuclear ribosomal 18S rRNA and the mitochondrial cytochrome c oxidase subunit I genes. The 18S rRNA data strongly suggest the presence of three species of terrestrial nemerteans in the Iberian Peninsula, an old landmass where terrestrial nemerteans had not previously been reported. These specimens originate from primarily undisturbed forests across a distance of c . 1000 km. Cytochrome c oxidase subunit I data also indicate the presence of multiple lineages of Iberian terrestrial nemerteans. Nonetheless, the pattern obtained from this marker is obscured most probably by deep genetic divergences. This molecular diversity, at least in some of the clades, suggests that the Iberian species are not the result of recent introductions, as proposed for other terrestrial nemerteans found in Europe. Our data also touch upon the question of a single origin of terrestriality in nemerteans, a hypothesis rejected by both data sets. Nevertheless, terrestriality seems to have had a single origin in the family Acteonemertidae. 相似文献
996.
997.
Phenological records as a complement to aerobiological data 总被引:1,自引:0,他引:1
Rafael Tormo Inmaculada Silva Ángela Gonzalo Alfonsa Moreno Remedios Pérez Santiago Fernández 《International journal of biometeorology》2011,55(1):51-65
Phenological studies in combination with aerobiological studies enable one to observe the relationship between the release
of pollen and its presence in the atmosphere. To obtain a suitable comparison between the daily variation of airborne pollen
concentrations and flowering, it is necessary for the level of accuracy of both sets of data to be as similar as possible.
To analyse the correlation between locally observed flowering data and pollen counts in pollen traps in order to set pollen
information forecasts, pollen was sampled using a Burkard volumetric pollen trap working continuously from May 1993. For the
phenological study we selected the main pollen sources of the six pollen types most abundant in our area: Cupressaceae, Platanus, Quercus, Plantago, Olea, and Poaceae with a total of 35 species. We selected seven sites to register flowering or pollination, two with semi-natural
vegetation, the rest being urban sites. The sites were visited weekly from March to June in 2007, and from January to June
in 2008 and 2009. Pollen shedding was checked at each visit, and recorded as the percentage of flowers or microsporangia in
that state. There was an association between flowering phenology and airborne pollen records for some of the pollen types
(Platanus, Quercus, Olea and Plantago). Nevertheless, for the other types (Cupressaceae and Poaceae) the flowering and airborne pollen peaks did not coincide,
with up to 1 week difference in phase. Some arguments are put forward in explanation of this phenomenon. Phenological studies
have shown that airborne pollen results from both local and distant sources, although the pollen peaks usually appear when
local sources are shedding the greatest amounts of pollen. Resuspension phenomena are probably more important than long-distance
transport in explaining the presence of airborne pollen outside the flowering period. This information could be used to improve
pollen forecasts. 相似文献
998.
Lake Magadi, an alkaline hypersaline lake in Kenya, is one of the most extreme water bodies known. Although its water temperatures often exceed 40°C, a particular lineage of ‘dwarf’ tilapia, Alcolapia grahami, has evolved remarkable adaptations to survive in this hostile environment. Magadi tilapia exists in small fragmented populations in isolated lagoons within Lake Magadi and its satellite Lake, Little Magadi. In spite of the potential this tilapia holds for understanding evolutionary processes in stressful environments, few genetic studies have focused on this species. We examined the genetic diversity and spatial genetic relationships of Magadi tilapia populations using microsatellite and mitochondrial markers. High levels of genetic variation were found to be supporting the hypothesis that A. grahami populations represent remnants of a much larger fish population that inhabited paleo-lake Orolonga. In contrast to previous studies, we found a well-supported genetic structure of A. grahami consisting of three differentiated genetic clusters (a) Little Magadi, (b) Fish Spring Lagoon and (c) Rest of Magadi. Given the importance of this species to the Magadi ecosystem and its potential evolutionary significance, the three genetic clusters should be considered as separate gene pools and conservation strategies aimed at protecting the species based on these clusters are recommended. 相似文献
999.
Daniel Prieto Gonzalo Aparicio Pablo E. Morande Flavio R. Zolessi 《Histochemistry and cell biology》2014,142(3):335-345
The increasing need for multiple-labeling of cells and whole organisms for fluorescence microscopy has led to the development of hundreds of fluorophores that either directly recognize target molecules or organelles, or are attached to antibodies or other molecular probes. DNA labeling is essential to study nuclear-chromosomal structure, as well as for gel staining, but also as a usual counterstain in immunofluorescence, FISH or cytometry. However, there are currently few reliable red to far-red-emitting DNA stains that can be used. We describe herein an extremely simple, inexpensive and robust method for DNA labeling of cells and electrophoretic gels using the very well-known histological stain methyl green (MG). MG used in very low concentrations at physiological pH proved to have relatively narrow excitation and emission spectra, with peaks at 633 and 677 nm, respectively, and a very high resistance to photobleaching. It can be used in combination with other common DNA stains or antibodies without any visible interference or bleed-through. In electrophoretic gels, MG also labeled DNA in a similar way to ethidium bromide, but, as expected, it did not label RNA. Moreover, we show here that MG fluorescence can be used as a stain for direct measuring of viability by both microscopy and flow cytometry, with full correlation to ethidium bromide staining. MG is thus a very convenient alternative to currently used red-emitting DNA stains. 相似文献
1000.