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61.
Cora E. Lewis John P. Bantle Alain G. Bertoni George Blackburn Frederick L. Brancati George A. Bray Lawrence J. Cheskin Jeffrey M. Curtis Caitlin Egan Mary Evans John P. Foreyt Siran Ghazarian Bethany Barone Gibbs Stephen P. Glasser Edward W. Gregg Helen P. Hazuda Louise Hesson James O. Hill Edward S. Horton Van S. Hubbard John M. Jakicic Robert W. Jeffery Karen C. Johnson Steven E. Kahn Abbas E. Kitabchi Dalane Kitzman William C. Knowler Edward Lipkin Sara Michaels Maria G. Montez David M. Nathan Ebenezer Nyenwe Jennifer Patricio Anne Peters Xavier Pi‐Sunyer Henry Pownall David M. Reboussin Donna H. Ryan Thomas A. Wadden Lynne E. Wagenknecht Holly Wyatt Rena R. Wing Susan Z. Yanovski 《Obesity (Silver Spring, Md.)》2020,28(2):247-258
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Margaret Burchinal Carollee Howes Robert Pianta Donna Bryant Diane Early Richard Clifford 《应用发育科学》2013,17(3):140-153
Publicly funded prekindergartens are programs that most states use to promote school readiness, especially of 4-year-old children at risk for academic problems due to poverty. Despite large public expenditures, these programs have not been widely evaluated. We examined 240 randomly selected pre-kindergarten programs in six states with mature programs that serve large numbers of children, and evaluated specific aspects of classroom quality and children's academic achievement in both the pre-kindergarten and kindergarten year for over 700 children. Results showed that, on average, pre-kindergarten teachers were moderately responsive and sensitive, but were less successful in engaging children in learning specific skills. Both sensitive and stimulating interactions with the teacher and the instructional quality aspects of the pre-kindergarten classroom predicted the acquisition of language, pre-academic, and social skills through the end of the kindergarten year. 相似文献
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Donna R. Curtis J. Hugh McDowell Paul A. Hargrave 《Preparative biochemistry & biotechnology》2013,43(2):83-102
A general method is described which allows the identification and preparation of peptides containing any amino acid of interest. The method has been applied to isolation of the methionyl peptides from a peptic digest of oxidized bovine rhodopsin. The peptide digestion mixture is first partially separated by ion exchange column chromatography. Location of peptides containing the desired amino acid is performed by amino acid analysis of acid hydrolyzed column fractions by high voltage paper electrophoresis. Peptides are further purified and prepared by peptide mapping, elution, and amino acid analysis using inexpensive high capacity techniques. Peptide sequencing is performed by a manual dansyl-Edman method well adapted for rapidly processing large numbers of samples. The methods are particularly well suited for detection and preparation of peptides containing amino acids for which there is no specific detection method. 相似文献
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Sounak Gupta Andrew M. Hau Jordan R. Beach Jyoti Harwalker Elisabetta Mantuano Steven L. Gonias Thomas T. Egelhoff Donna E. Hansel 《PloS one》2013,8(11)
Bladder cancer is the fourth most common cause of cancer in males in the United States. Invasive behavior is a major determinant of prognosis. In this study, we identified mammalian target of rapamycin complex 2 (mTORC2) as a central regulator of bladder cancer cell migration and invasion. mTORC2 activity was assessed by the extent of phosphorylation of Ser473 in AKT and determined to be approximately 5-fold higher in specimens of invasive human bladder cancer as opposed to non-invasive human bladder cancer. The immortalized malignant bladder cell lines, UMUC-3, J82 and T24 demonstrated higher baseline mTORC2 activity relative to the benign bladder papilloma-derived cell line RT4 and the normal urothelial cell line HU1. The malignant bladder cancer cells also demonstrated increased migration in transwell and denudation assays, increased invasion of matrigel, and increased capacity to invade human bladder specimens. Gene silencing of rictor, a critical component of mTORC2, substantially inhibited bladder cancer cell migration and invasion. This was accompanied by a significant decrease in Rac1 activation and paxillin phosphorylation. These studies identify mTORC2 as a major target for neutralizing bladder cancer invasion. 相似文献
68.
Weipeng Xiong S. Courtney Frasch Stacey M. Thomas Donna L. Bratton Peter M. Henson 《PloS one》2013,8(8)
Background/Objective
Phosphatidylserine (PS) exposed on apoptotic cells has been shown to stimulate production of transforming growth factor-β (TGF-β) and promote anti-inflammatory responses. However, the PS receptor(s) responsible for this induction has not been clearly determined.Methodology/Principal Findings
In the present study, using RAWTβRII cells in which a truncated dominant negative TGF-β receptor II was stably transfected in order to avoid auto-feedback induction of TGF-β, we show that TGF-β1 synthesis is initiated via activation of the scavenger receptor, CD36. The response requires exposure of PS on the apoptotic cell surface and was absent in macrophages lacking CD36. Direct activation of CD36 with an anti-CD36 antibody initiated TGF-β1 production, and signaling pathways involving both Lyn kinase and ERK1/2 were shown to participate in CD36-driven TGF-β1 expression.Conclusion/Significance
Since CD36 has been previously implicated in activation of secreted latent TGF-β, the present study indicates its role in the multiple steps to generation of this important biological mediator. 相似文献69.
Joanne Van Der Velden Grace Sum Donna Barker Emmanuel Koumoundouros Garry Barcham Heike Wulff Neil Castle Peter Bradding Kenneth Snibson 《PloS one》2013,8(6)
Background
The Ca2+-activated K+ channel KCa3.1 is expressed in several structural and inflammatory airway cell types and is proposed to play an important role in the pathophysiology of asthma. The aim of the current study was to determine whether inhibition of KCa3.1 modifies experimental asthma in sheep.Methodology and Principal Findings
Atopic sheep were administered either 30 mg/kg Senicapoc (ICA-17073), a selective inhibitor of the KCa3.1-channel, or vehicle alone (0.5% methylcellulose) twice daily (orally). Both groups received fortnightly aerosol challenges with house dust mite allergen for fourteen weeks. A separate sheep group received no allergen challenges or drug treatment. In the vehicle-control group, twelve weeks of allergen challenges resulted in a 60±19% increase in resting airway resistance, and this was completely attenuated by treatment with Senicapoc (0.25±12%; n = 10, P = 0.0147). The vehicle-control group had a peak-early phase increase in lung resistance of 82±21%, and this was reduced by 58% with Senicapoc treatment (24±14%; n = 10, P = 0.0288). Senicapoc-treated sheep also demonstrated reduced airway hyperresponsiveness, requiring a significantly higher dose of carbachol to increase resistance by 100% compared to allergen-challenged vehicle-control sheep (20±5 vs. 52±18 breath-units of carbachol; n = 10, P = 0.0340). Senicapoc also significantly reduced eosinophil numbers in bronchoalveolar lavage taken 48 hours post-allergen challenge, and reduced vascular remodelling.Conclusions
These findings suggest that KCa3.1-activity contributes to allergen-induced airway responses, inflammation and vascular remodelling in a sheep model of asthma, and that inhibition of KCa3.1 may be an effective strategy for blocking allergen-induced airway inflammation and hyperresponsiveness in humans. 相似文献70.
Estienne C. Swart John R. Bracht Vincent Magrini Patrick Minx Xiao Chen Yi Zhou Jaspreet S. Khurana Aaron D. Goldman Mariusz Nowacki Klaas Schotanus Seolkyoung Jung Robert S. Fulton Amy Ly Sean McGrath Kevin Haub Jessica L. Wiggins Donna Storton John C. Matese Lance Parsons Wei-Jen Chang Michael S. Bowen Nicholas A. Stover Thomas A. Jones Sean R. Eddy Glenn A. Herrick Thomas G. Doak Richard K. Wilson Elaine R. Mardis Laura F. Landweber 《PLoS biology》2013,11(1)
The macronuclear genome of the ciliate Oxytricha trifallax displays an extreme and unique eukaryotic genome architecture with extensive genomic variation. During sexual genome development, the expressed, somatic macronuclear genome is whittled down to the genic portion of a small fraction (∼5%) of its precursor “silent” germline micronuclear genome by a process of “unscrambling” and fragmentation. The tiny macronuclear “nanochromosomes” typically encode single, protein-coding genes (a small portion, 10%, encode 2–8 genes), have minimal noncoding regions, and are differentially amplified to an average of ∼2,000 copies. We report the high-quality genome assembly of ∼16,000 complete nanochromosomes (∼50 Mb haploid genome size) that vary from 469 bp to 66 kb long (mean ∼3.2 kb) and encode ∼18,500 genes. Alternative DNA fragmentation processes ∼10% of the nanochromosomes into multiple isoforms that usually encode complete genes. Nucleotide diversity in the macronucleus is very high (SNP heterozygosity is ∼4.0%), suggesting that Oxytricha trifallax may have one of the largest known effective population sizes of eukaryotes. Comparison to other ciliates with nonscrambled genomes and long macronuclear chromosomes (on the order of 100 kb) suggests several candidate proteins that could be involved in genome rearrangement, including domesticated MULE and IS1595-like DDE transposases. The assembly of the highly fragmented Oxytricha macronuclear genome is the first completed genome with such an unusual architecture. This genome sequence provides tantalizing glimpses into novel molecular biology and evolution. For example, Oxytricha maintains tens of millions of telomeres per cell and has also evolved an intriguing expansion of telomere end-binding proteins. In conjunction with the micronuclear genome in progress, the O. trifallax macronuclear genome will provide an invaluable resource for investigating programmed genome rearrangements, complementing studies of rearrangements arising during evolution and disease. 相似文献