全文获取类型
收费全文 | 1155篇 |
免费 | 69篇 |
专业分类
1224篇 |
出版年
2024年 | 1篇 |
2023年 | 10篇 |
2022年 | 25篇 |
2021年 | 50篇 |
2020年 | 14篇 |
2019年 | 32篇 |
2018年 | 42篇 |
2017年 | 22篇 |
2016年 | 44篇 |
2015年 | 73篇 |
2014年 | 85篇 |
2013年 | 115篇 |
2012年 | 121篇 |
2011年 | 111篇 |
2010年 | 51篇 |
2009年 | 58篇 |
2008年 | 70篇 |
2007年 | 76篇 |
2006年 | 58篇 |
2005年 | 39篇 |
2004年 | 31篇 |
2003年 | 29篇 |
2002年 | 22篇 |
2001年 | 7篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 6篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1980年 | 2篇 |
1976年 | 1篇 |
1973年 | 2篇 |
排序方式: 共有1224条查询结果,搜索用时 15 毫秒
21.
Social preferences like interpersonal altruism, fairness, reciprocity and inequity aversion are inherently linked to departures from pure self-interest. During economic interactions, for example, defectors may be punished even if this implies a cost for the punishers. This violation of canonical assumptions in economics indicates that socially oriented decisions may predominate over self-centred stances. Here we explore whether the personal experience of pain changes the balance between self-gain and socially based choices. We used laser stimulation to induce pain or a warm sensation in subjects playing a modified version of the Ultimatum Game (UG) both in the role of responder and proposer. After each shot, responders evaluated the fairness of the offer. Moreover, responders and proposers rated the intensity and unpleasantness of the sensation evoked by the laser stimulation. Results show that suffering proposers decrease fair offers and suffering responders increase their acceptance rate irrespective of economic offer. Crucially, the intensity of painful stimulation has a predictive role on Moderately Unfair offers' acceptance rates. Thus the personal experience of pain may favour the emergence of a self-centered perspective aimed at maximizing self-gain. The results suggest that bodily states play a fundamental role in higher-order interpersonal negotiations and interactions. 相似文献
22.
Background
Genome-wide association studies of pooled DNA samples were shown to be a valuable tool to identify candidate SNPs associated to a phenotype. No such study was up to now applied to childhood allergic asthma, even if the very high complexity of asthma genetics is an appropriate field to explore the potential of pooled GWAS approach.Methodology/Principal Findings
We performed a pooled GWAS and individual genotyping in 269 children with allergic respiratory diseases comparing allergic children with and without asthma. We used a modular approach to identify the most significant loci associated with asthma by combining silhouette statistics and physical distance method with cluster-adapted thresholding. We found 97% concordance between pooled GWAS and individual genotyping, with 36 out of 37 top-scoring SNPs significant at individual genotyping level. The most significant SNP is located inside the coding sequence of C5, an already identified asthma susceptibility gene, while the other loci regulate functions that are relevant to bronchial physiopathology, as immune- or inflammation-mediated mechanisms and airway smooth muscle contraction. Integration with gene expression data showed that almost half of the putative susceptibility genes are differentially expressed in experimental asthma mouse models.Conclusion/Significance
Combined silhouette statistics and cluster-adapted physical distance threshold analysis of pooled GWAS data is an efficient method to identify candidate SNP associated to asthma development in an allergic pediatric population. 相似文献23.
24.
Flavio De Maio Giuseppe Maulucci Mariachiara Minerva Saber Anoosheh Ivana Palucci Raffaella Iantomasi Valentina Palmieri Serena Camassa Michela Sali Maurizio Sanguinetti Wilbert Bitter Riccardo Manganelli Marco De Spirito Giovanni Delogu 《PloS one》2014,9(11)
PE_PGRS proteins are unique to the Mycobacterium tuberculosis complex and a number of other pathogenic mycobacteria. PE_PGRS30, which is required for the full virulence of M. tuberculosis (Mtb), has three main domains, i.e. an N-terminal PE domain, repetitive PGRS domain and the unique C-terminal domain. To investigate the role of these domains, we expressed a GFP-tagged PE_PGRS30 protein and a series of its functional deletion mutants in different mycobacterial species (Mtb, Mycobacterium bovis BCG and Mycobacterium smegmatis) and analysed protein localization by confocal microscopy. We show that PE_PGRS30 localizes at the mycobacterial cell poles in Mtb and M. bovis BCG but not in M. smegmatis and that the PGRS domain of the protein strongly contributes to protein cellular localization in Mtb. Immunofluorescence studies further showed that the unique C-terminal domain of PE_PGRS30 is not available on the surface, except when the PGRS domain is missing. Immunoblot demonstrated that the PGRS domain is required to maintain the protein strongly associated with the non-soluble cellular fraction. These results suggest that the repetitive GGA-GGN repeats of the PGRS domain contain specific sequences that contribute to protein cellular localization and that polar localization might be a key step in the PE_PGRS30-dependent virulence mechanism. 相似文献
25.
Fiorito Serena Collevecchio Chiara Epifano Francesco Genovese Salvatore Palumbo Lucia 《Phytochemistry Reviews》2023,22(1):73-84
Phytochemistry Reviews - Oxyprenylated secondary metabolites of plant, fungal, and microbial origin have emerged as biologically active natural compounds with a great potential for the next future.... 相似文献
26.
27.
Salvatore Cozzolino Serena Aceto Paolo Caputo Luciano Gaudio Roberto Nazzaro 《Nordic Journal of Botany》1998,18(1):79-87
A chloroplast DNA restriction fragment length polymorphism analysis has been carried out on representatives species of Orchis (Orchidaceae) and of the allied genera Aceras, Dactylorhiza , and Anacamptis . One species of Cephalanthera and one of Serapias were used as outgroups. The consensus tree from a cladistic analysis showed that Orchis , as presently defined, is paraphyletic, as it contains also Aceras anthropophorum and Dactylorhiza saccifera . The genus Orchis is divided in two clades: one including O. laxiflora, O. papilionacea, O. coriophora , and O. morio in a ladderized sequence, the other showing D. saccifera at the base, followed by a clade in which a collapse of O. mascula, O. pauciflora, O. quadripunctata is sister group to a clade composed by O. italica, O. simia , and A. anthropophorum . These results, which agree to a great extent with literature evidence on chromosomes and isozymes, have been compared with various traditional systematic hypotheses for the genus. 相似文献
28.
Francesca Ripamonti Luisa Albano Anna Rossini Serena Borrelli Sonia Fabris Roberto Mantovani Antonino Neri Andrea Balsari Alessandra Magnifico Elda Tagliabue 《Journal of cellular physiology》2013,228(4):871-878
Many squamous cell carcinomas (SCCs) are characterized by high levels of EGFR and by overexpression of the ΔNp63α isoform. Here, we investigated the regulation of ΔNp63α expression upon EGFR activation and the role of the EGFR–ΔNp63α axis in proliferation of SCC tumor‐initiating cells (TICs). SCC cell lines A‐431, Cal‐27, and SCC‐25 treated with EGF showed a time‐dependent increase in ΔNp63α expression at the protein and mRNA levels, which was blocked by the tyrosine kinase inhibitor (TKI) Lapatinib. RNA interference experiments suggested the role of STAT3 in regulating ΔNp63α expression downstream of EGFR. Inactivation of EGFR by the monoclonal antibody Cetuximab and RNA interference against STAT3 or ΔNp63α impaired the TICs ability to grow under non‐differentiating conditions. Radiation treatment, which triggers EGFR activation, induced ΔNp63α accumulation without affecting TICs proliferation, whereas the combination Cetuximab plus radiation significantly reduced TICs growth under non‐differentiating conditions. Together, our findings provide evidence that ΔNp63α expression is regulated by EGFR activation through STAT3 and that the EGFR–ΔNp63α axis is crucial for proliferation of TICs present in SCCs. J. Cell. Physiol. 228: 871–878, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
29.
The genetic component of human longevity: New insights from the analysis of pathway‐based SNP‐SNP interactions 下载免费PDF全文
Serena Dato Mette Soerensen Francesco De Rango Giuseppina Rose Kaare Christensen Lene Christiansen Giuseppe Passarino 《Aging cell》2018,17(3)
In human longevity studies, single nucleotide polymorphism (SNP) analysis identified a large number of genetic variants with small effects, yet not easily replicable in different populations. New insights may come from the combined analysis of different SNPs, especially when grouped by metabolic pathway. We applied this approach to study the joint effect on longevity of SNPs belonging to three candidate pathways, the insulin/insulin‐like growth factor signalling (IIS), DNA repair and pro/antioxidant. We analysed data from 1,058 tagging SNPs in 140 genes, collected in 1825 subjects (1,089 unrelated nonagenarians from the Danish 1905 Birth Cohort Study and 736 Danish controls aged 46–55 years) for evaluating synergic interactions by SNPsyn. Synergies were further tested by the multidimensional reduction (MDR) approach, both intra‐ and interpathways. The best combinations (FDR<0.0001) resulted those encompassing IGF1R‐rs12437963 and PTPN1‐rs6067484, TP53‐rs2078486 and ERCC2‐rs50871, TXNRD1‐rs17202060 and TP53‐rs2078486, the latter two supporting a central role of TP53 in mediating the concerted activation of the DNA repair and pro‐antioxidant pathways in human longevity. Results were consistently replicated with both approaches, as well as a significant effect on longevity was found for the GHSR gene, which also interacts with partners belonging to both IIS and DNA repair pathways (PAPPA, PTPN1, PARK7, MRE11A). The combination GHSR‐MREA11, positively associated with longevity by MDR, was further found influencing longitudinal survival in nonagenarian females (p = .026). Results here presented highlight the validity of SNP‐SNP interactions analyses for investigating the genetics of human longevity, confirming previously identified markers but also pointing to novel genes as central nodes of additional networks involved in human longevity. 相似文献
30.