全文获取类型
收费全文 | 4981篇 |
免费 | 340篇 |
国内免费 | 1篇 |
出版年
2023年 | 34篇 |
2022年 | 72篇 |
2021年 | 121篇 |
2020年 | 88篇 |
2019年 | 104篇 |
2018年 | 116篇 |
2017年 | 98篇 |
2016年 | 171篇 |
2015年 | 260篇 |
2014年 | 293篇 |
2013年 | 378篇 |
2012年 | 454篇 |
2011年 | 381篇 |
2010年 | 266篇 |
2009年 | 230篇 |
2008年 | 315篇 |
2007年 | 302篇 |
2006年 | 273篇 |
2005年 | 234篇 |
2004年 | 195篇 |
2003年 | 206篇 |
2002年 | 161篇 |
2001年 | 48篇 |
2000年 | 48篇 |
1999年 | 47篇 |
1998年 | 27篇 |
1997年 | 28篇 |
1996年 | 35篇 |
1995年 | 30篇 |
1994年 | 23篇 |
1993年 | 25篇 |
1992年 | 31篇 |
1991年 | 26篇 |
1990年 | 21篇 |
1989年 | 21篇 |
1988年 | 17篇 |
1987年 | 11篇 |
1986年 | 15篇 |
1985年 | 15篇 |
1984年 | 9篇 |
1983年 | 6篇 |
1982年 | 9篇 |
1981年 | 6篇 |
1980年 | 9篇 |
1979年 | 10篇 |
1978年 | 9篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1973年 | 8篇 |
1966年 | 4篇 |
排序方式: 共有5322条查询结果,搜索用时 31 毫秒
161.
Paola Ulivi Laura Mercatali Gian-Luca Casoni Emanuela Scarpi Lauro Bucchi Rosella Silvestrini Stefano Sanna Marco Monteverde Dino Amadori Venerino Poletti Wainer Zoli 《PloS one》2013,8(2)
Background
Non-invasive early detection of lung cancer could reduce the number of patients diagnosed with advanced disease, which is associated with a poor prognosis. We analyzed the diagnostic accuracy of a panel of peripheral blood markers in detecting non small cell lung cancer (NSCLC).Methods
100 healthy donors and 100 patients with NSCLC were enrolled onto this study. Free circulating DNA, circulating mRNA expression of peptidylarginine deiminase type 4 (PAD4/PADI4), pro-platelet basic protein (PPBP) and haptoglobin were evaluated using a Real-Time PCR-based method.Results
Free circulating DNA, PADI4, PPBP and haptoglobin levels were significantly higher in NSCLC patients than in healthy donors (p<0.0001, p<0.0001, p = 0.0002 and p = 0.0001, respectively). The fitted logistic regression model demonstrated a significant direct association between marker expression and lung cancer risk. The odds ratios of individual markers were 6.93 (95% CI 4.15–11.58; p<0.0001) for free DNA, 6.99 (95% CI 3.75–13.03; p<0.0001) for PADI4, 2.85 (95% CI 1.71–4.75; p<0.0001) for PPBP and 1.16 (95% CI 1.01–1.33; p = 0.031) for haptoglobin. Free DNA in combination with PPBP and PADI4 gave an area under the ROC curve of 0.93, 95% CI = 0.90–0.97, with sensitivity and specificity over 90%.Conclusions
Free circulating DNA analysis combined with PPBP and PADI4 expression determination appears to accurately discriminate between healthy donors and NSCLC patients. This non-invasive multimarker approach warrants further research to assess its potential role in the diagnostic or screening workup of subjects with suspected lung cancer. 相似文献162.
Irina Lonskaya John Partridge Rupa R. Lalchandani Andrew Chung Taehee Lee Stefano Vicini Hyang-Sook Hoe Seung T. Lim Katherine Conant 《PloS one》2013,8(7)
Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases that can be released from neurons in an activity dependent manner to play a role in varied forms of learning and memory. MMP inhibitors impair hippocampal long term potentiation (LTP), spatial memory, and behavioral correlates of drug addiction. Since MMPs are thought to influence LTP through a β1 integrin dependent mechanism, it has been suggested that these enzymes cleave specific substrates to generate integrin binding ligands. In previously published work, we have shown that neuronal activity stimulates rapid MMP dependent shedding of intercellular adhesion molecule-5 (ICAM-5), a synaptic adhesion molecule expressed on dendrites of the telencephalon. We have also shown that the ICAM-5 ectodomain can interact with β1 integrins to stimulate integrin dependent phosphorylation of cofilin, an event that occurs with dendritic spine maturation and LTP. In the current study, we investigate the potential for the ICAM-5 ectodomain to stimulate changes in α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) dependent glutamatergic transmission. Single cell recordings show that the ICAM-5 ectodomain stimulates an increase in the frequency, but not the amplitude, of AMPA mini excitatory post synaptic currents (mEPSCs). With biotinylation and precipitation assays, we also show that the ICAM-5 ectodomain stimulates an increase in membrane levels of GluA1, but not GluA2, AMPAR subunits. In addition, we observe an ICAM-5 associated increase in GluA1 phosphorylation at serine 845. Concomitantly, ICAM-5 affects an increase in GluA1 surface staining along dendrites without affecting an increase in dendritic spine number. Together these data are consistent with the possibility that soluble ICAM-5 increases glutamatergic transmission and that post-synaptic changes, including increased phosphorylation and dendritic insertion of GluA1, could contribute. We suggest that future studies are warranted to determine whether ICAM-5 is one of a select group of synaptic CAMs whose shedding contributes to MMP dependent effects on learning and memory. 相似文献
163.
Lorenzo Tancioni Tommaso Russo Stefano Cataudella Valentina Milana Anne Kathrin Hett Elisa Corsi Anna Rita Rossi 《PloS one》2013,8(4)
Leuciscine fishes represent an important component of freshwater ichthyofauna endemic to northern Mediterranean areas. This lineage shows high intra-specific morphological variability and exhibits high levels of hybridization, two characteristics that contribute to systematic uncertainties, misclassification of taxa and, potentially, the mismanagement of biodiversity. This study focused on brook chub, Squalius lucumonis, an endemic taxon of Central Italy. The taxonomic status of this species has long been questioned, and a hybrid origin from sympatric leusciscines (S. squalus x Rutilus rubilio, or S. squalus x Telestes muticellus) has been hypothesised. A phenotypic (evaluating shape and meristic counts) and genetic (using mitochondrial and nuclear markers) investigation of these four taxa was conducted to test species delimitation in sympatric areas and to evaluate the taxonomic status of S. lucumonis. One hundred and forty-five individuals of all four taxa were collected within streams of the lowest portion of the Tiber River basin and analysed; this region encompasses a large portion of the S. lucumonis distribution. The different morphological and genetic approaches were individually examined, compared, and then combined in a quantitative model to both investigate the limits of each approach and to identify cases of misclassification. The results obtained confirm the cladogenetic non-hybrid origin of S. lucumonis, highlight the need for immediate conservation actions and emphasise the value of an integrated approach in the study of leuciscines evolution. 相似文献
164.
Stefano Amente Luigi LaniaBarbara Majello 《Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms》2013,1829(10):981-986
DNA and histone chromatin modifying enzymes play a crucial role in chromatin remodeling in several biological processes. Lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, is a relevant player in the regulation of a broad spectrum of biological processes including development, cellular differentiation, embryonic pluripotency and cancer. Here, we review recent insights on the role of LSD1 activity in chromatin regulatory complexes, its functional role in the epigenetic changes during embryonic development, in the establishment and maintenance of stemness and during cancer progression. 相似文献
165.
Alcohol consumption and alcohol problems after bariatric surgery in the swedish obese subjects study
166.
Irene Cardinali Hovirag Lancioni Andrea Giontella Marco Rosario Capodiferro Stefano Capomaccio Luca Buttazzoni Giovanni Paolo Biggio Raffaele Cherchi Emidio Albertini Anna Olivieri Katia Cappelli Alessandro Achilli Maurizio Silvestrelli 《PloS one》2016,11(4)
BackgroundThe climatic and cultural diversity of the Italian Peninsula triggered, over time, the development of a great variety of horse breeds, whose origin and history are still unclear. To clarify this issue, analyses on phenotypic traits and genealogical data were recently coupled with molecular screening.MethodologyTo provide a comprehensive overview of the horse genetic variability in Italy, we produced and phylogenetically analyzed 407 mitochondrial DNA (mtDNA) control-region sequences from ten of the most important Italian riding horse and pony breeds: Bardigiano, Esperia, Giara, Lipizzan, Maremmano, Monterufolino, Murgese, Sarcidano, Sardinian Anglo-Arab, and Tolfetano. A collection of 36 Arabian horses was also evaluated to assess the genetic consequences of their common use for the improvement of some local breeds.ConclusionsIn Italian horses, all previously described domestic mtDNA haplogroups were detected as well as a high haplotype diversity. These findings indicate that the ancestral local mares harbored an extensive genetic diversity. Moreover, the limited haplotype sharing (11%) with the Arabian horse reveals that its impact on the autochthonous mitochondrial gene pools during the final establishment of pure breeds was marginal, if any. The only significant signs of genetic structure and differentiation were detected in the geographically most isolated contexts (i.e. Monterufolino and Sardinian breeds). Such a geographic effect was also confirmed in a wider breed setting, where the Italian pool stands in an intermediate position together with most of the other Mediterranean stocks. However, some notable exceptions and peculiar genetic proximities lend genetic support to historical theories about the origin of specific Italian breeds. 相似文献
167.
Paola Ruffa Stefano Raimondi Paolo Boccacci Simona Abbà Anna Schneider 《Tree Genetics & Genomes》2016,12(3):50
A great number of flavored grape varieties, of significant oenological potential, are traditionally cultivated in north-western Italy, besides the renowned “Moscato bianco” (syn. “Muscat à petits grains blancs”). Understanding their origin, besides its historical and scientific interest, would help to increase market appeal and consequently facilitate the commercial exploitation of these products. Twenty-four aromatic genotypes were investigated for their identity, kinship relations, and genetic origins through molecular markers (SSR and SNPs) supported by plant morphology and historical information. Flavored grape genotypes from other regions, possible ancestors, and reference cultivars of known pedigree were also included in the analysis. Kinship analysis used a likelihood-based approach (IBS, IBD, relatedness coefficients, and likelihood ratios) to achieve strong statistical support. The analyses revealed two possible leading genitors, in turn closely related by a parent/offspring relationship: “Moscato bianco” and “Malvasia aromatica di Parma,” a female grape cultivar that is today almost extinct. The outlined molecular and statistical approach could be applied for the investigation on the origin of ancient traditional cultivars of other vegetative propagated species. 相似文献
168.
Stefano Minguzzi Federica Terlizzi Chiara Lanzoni Carlo Poggi Pollini Claudio Ratti 《PloS one》2016,11(1)
Many efforts have been made to develop a rapid and sensitive method for phytoplasma and virus detection. Taking our cue from previous works, different rapid sample preparation methods have been tested and applied to Candidatus Phytoplasma prunorum (‘Ca. P. prunorum’) detection by RT-qPCR. A duplex RT-qPCR has been optimized using the crude sap as a template to simultaneously amplify a fragment of 16S rRNA of the pathogen and 18S rRNA of the host plant. The specific plant 18S rRNA internal control allows comparison and relative quantification of samples. A comparison between DNA and RNA contribution to qPCR detection is provided, showing higher contribution of the latter. The method presented here has been validated on more than a hundred samples of apricot, plum and peach trees. Since 2013, this method has been successfully applied to monitor ‘Ca. P. prunorum’ infections in field and nursery. A triplex RT-qPCR assay has also been optimized to simultaneously detect ‘Ca. P. prunorum’ and Plum pox virus (PPV) in Prunus. 相似文献
169.
Stefano Palminteri Emma J. Kilford Giorgio Coricelli Sarah-Jayne Blakemore 《PLoS computational biology》2016,12(6)
Adolescence is a period of life characterised by changes in learning and decision-making. Learning and decision-making do not rely on a unitary system, but instead require the coordination of different cognitive processes that can be mathematically formalised as dissociable computational modules. Here, we aimed to trace the developmental time-course of the computational modules responsible for learning from reward or punishment, and learning from counterfactual feedback. Adolescents and adults carried out a novel reinforcement learning paradigm in which participants learned the association between cues and probabilistic outcomes, where the outcomes differed in valence (reward versus punishment) and feedback was either partial or complete (either the outcome of the chosen option only, or the outcomes of both the chosen and unchosen option, were displayed). Computational strategies changed during development: whereas adolescents’ behaviour was better explained by a basic reinforcement learning algorithm, adults’ behaviour integrated increasingly complex computational features, namely a counterfactual learning module (enabling enhanced performance in the presence of complete feedback) and a value contextualisation module (enabling symmetrical reward and punishment learning). Unlike adults, adolescent performance did not benefit from counterfactual (complete) feedback. In addition, while adults learned symmetrically from both reward and punishment, adolescents learned from reward but were less likely to learn from punishment. This tendency to rely on rewards and not to consider alternative consequences of actions might contribute to our understanding of decision-making in adolescence. 相似文献
170.
Sonia Vallet Muhammad Hasan Bashari Feng-Juan Fan Stefano Malvestiti Andreas Schneeweiss Patrick Wuchter Dirk J?ger Klaus Podar 《PloS one》2016,11(3)