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991.
Su Yon Jung Mara Z. Vitolins Jenifer Fenton Alexis C. Frazier-Wood Stephen D. Hursting Shine Chang 《PloS one》2015,10(3)
Purpose
Risk factors for obesity and weight gain are typically evaluated individually while “adjusting for” the influence of other confounding factors, and few studies, if any, have created risk profiles by clustering risk factors. We identified subgroups of postmenopausal women homogeneous in their clustered modifiable and non-modifiable risk factors for gaining ≥ 3% weight.Methods
This study included 612 postmenopausal women 50–79 years old, enrolled in an ancillary study of the Women''s Health Initiative Observational Study between February 1995 and July 1998. Classification and regression tree and stepwise regression models were built and compared.Results
Of 27 selected variables, the factors significantly related to ≥ 3% weight gain were weight change in the past 2 years, age at menopause, dietary fiber, fat, alcohol intake, and smoking. In women younger than 65 years, less than 4 kg weight change in the past 2 years sufficiently reduced risk of ≥ 3% weight gain. Different combinations of risk factors related to weight gain were reported for subgroups of women: women 65 years or older (essential factor: < 9.8 g/day dietary factor), African Americans (essential factor: currently smoking), and white women (essential factor: ≥ 5 kg weight change for the past 2 years).Conclusions
Our findings suggest specific characteristics for particular subgroups of postmenopausal women that may be useful for identifying those at risk for weight gain. The study results may be useful for targeting efforts to promote strategies to reduce the risk of obesity and weight gain in subgroups of postmenopausal women and maximize the effect of weight control by decreasing obesity-relevant adverse health outcomes. 相似文献992.
Pathogenicity of the human pathogen Helicobacter pylori relies on its capacity to adapt to a hostile environment and to escape the host response. Although there have been great advances in our understanding of the bacterial cytoskeleton, major gaps remain in our knowledge of its contribution to virulence. In this study we have explored the influence of coiled coil rich proteins (Ccrp) cytoskeletal elements on pathogenicity factors of H. pylori. Deletion of any of the ccrp resulted in a strongly decreased activity of the main pathogenicity factor urease. We further investigated their role using in vitro co-culture experiments with the human gastric adenocarcinoma cell line AGS modeling H. pylori - host cell interactions. Intriguingly, host cell showed only a weak “scattering/hummingbird” phenotype, in which host cells are transformed from a uniform polygonal shape into a severely elongated state characterized by the formation of needle-like projections, after co-incubation with any ccrp deletion mutant. Furthermore, co-incubation with the ccrp59 mutant resulted in reduced type IV secretion system associated activities, e.g. IL-8 production and CagA translocation/phosphorylation. Thus, in addition to their role in maintaining the helical cell shape of H. pylori Ccrp proteins influence many cellular processes and are thereby crucial for the virulence of this human pathogen. 相似文献
993.
Ellen Binder Dipa Natarajan Julie Cooper Rania Kronfli Mara Cananzi Jean-Marie Delalande Conor McCann Alan J. Burns Nikhil Thapar 《PloS one》2015,10(3)
Objectives
Enteric neural stem cells provide hope of curative treatment for enteric neuropathies. Current protocols for their harvesting from humans focus on the generation of ‘neurospheres’ from cultures of dissociated gut tissue. The study aims to better understand the derivation, generation and composition of enteric neurospheres.Design
Gut tissue was obtained from Wnt1-Cre;Rosa26Yfp/Yfp transgenic mice (constitutively labeled neural crest cells) and paediatric patients. Gut cells were cultured either unsorted (mixed neural crest/non-neural crest), or following FACS selection into neural crest (murine-YFP+ve/human-p75+ve) or non-neural crest (YFP-ve/p75-ve) populations. Cultures and resultant neurospheres were characterized using immunolabelling in vitro and following transplantation in vivo.Results
Cultures of (i) unsorted, (ii) neural crest, and (iii) non-neural crest cell populations generated neurospheres similar in numbers, size and morphology. Unsorted neurospheres were highly heterogeneous for neural crest content. Neural crest-derived (YFP+ve/p75+ve) neurospheres contained only neural derivatives (neurons and glia) and were devoid of non-neural cells (i.e. negative for SMA, c-Kit), with the converse true for non-neural crest-derived (YFP-ve/p75-ve) ‘neurospheres’. Under differentiation conditions only YFP+ve cells gave rise to neural derivatives. Both YFP+ve and YFP-ve cells displayed proliferation and spread upon transplantation in vivo, but YFP-ve cells did not locate or integrate within the host ENS.Conclusions
Spherical accumulations of cells, so-called ‘neurospheres’ forming in cultures of dissociated gut contain variable proportions of neural crest-derived cells. If they are to be used for ENS cell replacement therapy then improved protocols for their generation, including cell selection, should be sought in order to avoid inadvertent transplantation of non-therapeutic, non-ENS cells. 相似文献994.
Carole Laffont Thomas Rey Olivier André Mara Novero Théophile Kazmierczak Frédéric Debellé Paola Bonfante Christophe Jacquet Florian Frugier 《PloS one》2015,10(1)
Cytokinins are phytohormones that regulate many developmental and environmental responses. The Medicago truncatula cytokinin receptor MtCRE1 (Cytokinin Response 1) is required for the nitrogen-fixing symbiosis with rhizobia. As several cytokinin signaling genes are modulated in roots depending on different biotic and abiotic conditions, we assessed potential involvement of this pathway in various root environmental responses. Phenotyping of cre1 mutant roots infected by the Gigaspora margarita arbuscular mycorrhizal (AM) symbiotic fungus, the Aphanomyces euteiches root oomycete, or subjected to an abiotic stress (salt), were carried out. Detailed histological analysis and quantification of cre1 mycorrhized roots did not reveal any detrimental phenotype, suggesting that MtCRE1 does not belong to the ancestral common symbiotic pathway shared by rhizobial and AM symbioses. cre1 mutants formed an increased number of emerged lateral roots compared to wild-type plants, a phenotype which was also observed under non-stressed conditions. In response to A. euteiches, cre1 mutants showed reduced disease symptoms and an increased plant survival rate, correlated to an enhanced formation of lateral roots, a feature previously linked to Aphanomyces resistance. Overall, we showed that the cytokinin CRE1 pathway is not only required for symbiotic nodule organogenesis but also affects both root development and resistance to abiotic and biotic environmental stresses. 相似文献
995.
Christopher C. Valley Donna J. Arndt-Jovin Narain Karedla Mara P. Steinkamp Alexey I. Chizhik William S. Hlavacek Bridget S. Wilson Keith A. Lidke Diane S. Lidke 《Molecular biology of the cell》2015,26(22):4087-4099
Mutations within the epidermal growth factor receptor (EGFR/erbB1/Her1) are often associated with tumorigenesis. In particular, a number of EGFR mutants that demonstrate ligand-independent signaling are common in non–small cell lung cancer (NSCLC), including kinase domain mutations L858R (also called L834R) and exon 19 deletions (e.g., ΔL747-P753insS), which collectively make up nearly 90% of mutations in NSCLC. The molecular mechanisms by which these mutations confer constitutive activity remain unresolved. Using multiple subdiffraction-limit imaging modalities, we reveal the altered receptor structure and interaction kinetics of NSCLC-associated EGFR mutants. We applied two-color single quantum dot tracking to quantify receptor dimerization kinetics on living cells and show that, in contrast to wild-type EGFR, mutants are capable of forming stable, ligand-independent dimers. Two-color superresolution localization microscopy confirmed ligand-independent aggregation of EGFR mutants. Live-cell Förster resonance energy transfer measurements revealed that the L858R kinase mutation alters ectodomain structure such that unliganded mutant EGFR adopts an extended, dimerization-competent conformation. Finally, mutation of the putative dimerization arm confirmed a critical role for ectodomain engagement in ligand-independent signaling. These data support a model in which dysregulated activity of NSCLC-associated kinase mutants is driven by coordinated interactions involving both the kinase and extracellular domains that lead to enhanced dimerization. 相似文献
996.
Daniel P. Miller Hana Hall Ryan Chaparian Madison Mara Alison Mueller Mark C. Hall Katie B. Shannon 《Molecular biology of the cell》2015,26(16):2913-2926
Cytokinesis separates cells by contraction of a ring composed of filamentous actin (F-actin) and type II myosin. Iqg1, an IQGAP family member, is an essential protein in Saccharomyces cerevisiae required for assembly and contraction of the actomyosin ring. Localization of F-actin to the ring occurs only after anaphase and is mediated by the calponin homology domain (CHD) of Iqg1, but the regulatory mechanisms that temporally restrict actin ring assembly are not well defined. We tested the hypothesis that dephosphorylation of four perfect cyclin-dependent kinase (Cdk) sites flanking the CHD promotes actin ring formation, using site-specific alanine mutants. Cells expressing the nonphosphorylatable iqg1-4A allele formed actin rings before anaphase and exhibited defects in myosin contraction and cytokinesis. The Cdc14 phosphatase is required for normal cytokinesis and acts on specific Cdk phosphorylation sites. Overexpression of Cdc14 resulted in premature actin ring assembly, whereas inhibition of Cdc14 function prevented actin ring formation. Cdc14 associated with Iqg1, dependent on several CHD-flanking Cdk sites, and efficiently dephosphorylated these sites in vitro. Of importance, the iqg1-4A mutant rescued the inability of cdc14-1 cells to form actin rings. Our data support a model in which dephosphorylation of Cdk sites around the Iqg1 CHD by Cdc14 is both necessary and sufficient to promote actin ring formation. Temporal control of actin ring assembly by Cdk and Cdc14 may help to ensure that cytokinesis onset occurs after nuclear division is complete. 相似文献
997.
Restoring for the present or restoring for the future: enhanced performance of two sympatric oaks (Quercus ilex and Quercus pyrenaica) above the current forest limit
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Alexandro B. Leverkus Jorge Castro Manuel J. Delgado‐Capel Carlos Molinas‐González Manuel Pulgar Sara Marañón‐Jiménez Antonio Delgado‐Huertas José I. Querejeta 《Restoration Ecology》2015,23(6):936-946
Reforestation is common to restore degraded ecosystems, but tree‐species choice often neglects ongoing environmental changes. We evaluated the performance of planted seedlings of two oak species at two sites in a Mediterranean mountain (Sierra Nevada, SE Spain): one located within the current altitudinal forest range (1,600–1,760 m), and one above the upper forest limit (1,970–2,120 m). The forest service planted 1,350 seedlings of the deciduous Pyrenean oak and the evergreen Holm oak in a postfire successional shrubland. After 2 years, seedlings were monitored for survival, and a subset of 110 Pyrenean oaks and 185 Holm oaks were harvested for analyses of biomass and foliar nutrient status, δ13C, and δ18O. Both species showed the highest survival and leaf N status above the upper forest limit, and survival increased with altitude within each plot. The deciduous oak benefited most from planting at higher altitude, and it also had greater biomass at the higher site. Correlations between foliar N, δ18O, and δ13C across elevations indicate tighter stomatal control of water loss and greater water‐use efficiency with increasing plant N status at higher altitude, which may represent a so‐far overlooked positive feedback mechanism that could foster uphill range shifts in water‐limited mountain regions. Given ongoing trends and future projections of increasing temperature and aridity throughout the Mediterranean region, tree‐species selection for forest restoration should target forecasted climatic conditions rather than those prevailing in the past. This study highlights that ecosystem restoration provides an opportunity to assist species range shifts under rapidly changing climate. 相似文献
998.
The double inhibition of endogenously produced BMP and Wnt factors synergistically triggers dorsal telencephalic differentiation of mouse ES cells
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Michele Bertacchi Luca Pandolfini Mara D'Onofrio Rossella Brandi Federico Cremisi 《Developmental neurobiology》2015,75(1):66-79
Embryonic stem (ES) cells are becoming a popular model of in vitro neurogenesis, as they display intrinsic capability to generate neural progenitors that undergo the known steps of in vivo neural development. These include the acquisition of distinct regional fates, which depend on growth factors and signals that are present in the culture medium. The control of the intracellular signaling that is active at different steps of ES cell neuralization, even when cells are cultured in chemically defined medium, is complicated by the endogenous production of growth factors. However, this endogenous production has been poorly investigated so far. To address this point, we performed a high‐throughput analysis of the expression of morphogens during mouse ES cell neuralization in minimal medium. We found that during their neuralization, ES cells increased the expression of members of Wnt, Fibroblast Growth Factor (FGF), and BMP families. Conversely, the expression of Activin/Nodal and Shh ligands was low in early steps of neuralization. In this experimental condition, neural progenitors and neurons generated by ES cells expressed a gene expression profile that was consistent with a midbrain identity. We found that endogenous BMP and Wnt signaling, but not FGF signaling, synergistically affected ES cell neural patterning, by turning off a profile of dorsal/telencephalic gene expression. Double BMP and Wnt inhibition allowed neuralized ES cells to sequentially activate key genes of cortical differentiation. Our findings are consistent with a novel synergistic effect of Wnt and BMP endogenous signaling of ES cells in inhibiting a cortical differentiation program. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 66–79, 2015 相似文献
999.
Thomas Pollet Olivier Cloutier Christian Nozais Christopher W. McKindsey Philippe Archambault 《PloS one》2015,10(4)
This experimental microcosm study reports the influence of organic enrichments by mussel biodeposits on the metabolic activity and functional diversity of benthic prokaryotic communities. The different biodeposit enrichment regimes created, which mimicked the quantity of faeces and pseudo-faeces potentially deposited below mussel farms, show a clear stimulatory effect of this organic enrichment on prokaryotic metabolic activity. This effect was detected once a certain level of biodeposition was attained with a tipping point estimated between 3.25 and 10 g day-1 m-2. Prokaryotic communities recovered their initial metabolic activity by 11 days after the cessation of biodeposit additions. However, their functional diversity remained greater than prior to the disturbance suggesting that mussel biodeposit enrichment may disturb the functioning and perhaps the role of prokaryotic communities in benthic ecosystems. This manipulative approach provided new information on the influence of mussel biodeposition on benthic prokaryotic communities and dose-response relationships and may support the development of carrying capacity models for bivalve culture. 相似文献
1000.
Cecilia Bozzetti Federico Quaini Anna Squadrilli Marcello Tiseo Caterina Frati Costanza Lagrasta Cinzia Azzoni Lorena Bottarelli Maricla Galetti Angela Alama Silvana Belletti Rita Gatti Antonio Passaro Angela Gradilone Andrea Cavazzoni Roberta Alfieri Pier Giorgio Petronini Mara Bonelli Angela Falco Cecilia Carubbi Giuseppe Pedrazzi Rita Nizzoli Nadia Naldi Carmine Pinto Andrea Ardizzoni 《PloS one》2015,10(11)