全文获取类型
收费全文 | 1154篇 |
免费 | 69篇 |
专业分类
1223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 | 69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1223条查询结果,搜索用时 15 毫秒
81.
Del Bo R Scarlato M Ghezzi S Maestroni A Sjölind L Forsblom C Wessman M Groop PH Comi GP Bresolin N Luzi L Zerbini G 《Immunogenetics》2006,58(2-3):107-112
Vascular endothelial growth factor (VEGF) is a multifunctional cytokine originally described as an angiogenic factor. A number of reports have recently demonstrated that VEGF increases pancreatic islet survival after islet transplantation by stimulating angiogenesis and improving islet revascularization. Whether VEGF can protect from the autoimmune destruction of insulin-producing beta-cells that characterizes the development of type 1 diabetes is presently unknown. To clarify this issue, we studied the association of three polymorphisms of the promoter region of VEGF with type 1 diabetes in the Italian and the Finnish populations. The polymorphisms considered [C(-2578)A, G(-1190)A, and G(-1154)A] are known to modulate in vitro and in vivo VEGF expression. We found that VEGF promoter genotypes are associated with type 1 diabetes in both populations, but with different combinations. In Italian individuals, the -2578AA and -1190AA genotypes are associated with type 1 diabetes and accelerate its onset, while in Finnish individuals, -1154GG and -1190GG protect from type 1 diabetes and delay its onset. In conclusion, because the expected functional consequence of both genotype combinations is a reduced VEGF expression in diabetic patients, we propose a protective role of VEGF in the development of type 1 diabetes. 相似文献
82.
Female dark‐eyed juncos Junco hyemalis thurberi produce male‐like song in a territorial context during the early breeding season 下载免费PDF全文
Dustin G. Reichard Daniel E. Brothers Serena E. George Jonathan W. Atwell Ellen D. Ketterson 《Journal of avian biology》2018,49(2)
Reports of female song, once considered a rarity, have recently increased across a variety of avian taxa. Females of many species can be induced to produce male‐like song with exogenous testosterone, but observations of female song in free‐living birds remain limited by incomplete sampling of females. Here, we report three independent observations of female dark‐eyed juncos Junco hyemalis producing male‐like song early in the breeding season (i.e. post‐territory establishment, pre‐nesting) in a recently established non‐migratory, urban population. To elicit song, we presented 17 free‐living junco pairs with a live, caged female conspecific. Three unique females responded to our trials by diving at the intruding female, chasing their (male) mate, fanning their tail feathers, and singing a trilled song similar in structure to male long‐range (broadcast) song. We compared male and female songs quantitatively and found that the two sexes were statistically similar in many spectral and temporal characteristics, but female songs had significantly lower minimum and peak frequencies than males. This result is particularly surprising, as males in this urban population are known to sing at a significantly higher minimum frequency than males in a nearby montane population. Both the seasonal and social context in which these songs were observed suggest a potential function for female song in mate guarding and polygyny prevention, but more data are needed to test this hypothesis. Whether female song is common in all dark‐eyed juncos during the early breeding season or if it is restricted to this particular urban and non‐migratory population remains an important question for future research. 相似文献
83.
Serena Imazio David Maghradze Gabriella De Lorenzis Roberto Bacilieri Valérie Laucou Patrice This Attilio Scienza Osvaldo Failla 《Tree Genetics & Genomes》2013,9(3):641-658
Historical information and archaeological and palaeobotanical findings point Georgia, in the South Caucasus, as a cradle for grapevine (Vitis vinifera L.) domestication from its wild form (V. vinifera silvestris Beck.) and subsequent selection and development of varieties with characters suitable for human consumption. The hypothesis of Georgia being a center of domestication, combined with its distance from western countries and the importance of its viticulture and wine production, make Georgian grape germplasm particularly interesting to be investigated under the genetic point of view. Twenty nuclear microsatellite loci were used to genotype 112 Georgian grapevine accessions (V. vinifera sativa Beck.) from germplasm collections and 18 from spontaneous growing plants (V. vinifera silvestris Beck.) found in wild conditions and to compare them to a large international cultivar collection in France. Data analysis shows that Georgian grapevine germplasm has maintained distinctive traits despite arrival of international, foreign varieties and still conserve characteristics of local breeding linked to traditional wine production regions of the country. Results have identified alleles, overall loci, well represented in the Georgian germplasm (cultivated and wild) and absent or poorly represented in other countries, highlighting uniqueness and originality of traits of this viticulture. Moreover, the search for relationships between Georgian and foreign viticulture has evidenced few interesting cases linking the Georgian varieties with Western European ones and with neighboring Caucasian countries, helping to identify the real place of origin in some doubtful cases. In addition, populations or sparse individuals of wild grapevine still preserved in the Georgian natural environments present smaller genetic distances with local cultivars than in other European regions. Principal component analysis (PCA) has also identified special overlapping of the wild compartment with some cultivated varieties. This work provides a highly significant new contribution to applied aspects of Georgian grapevine genetic resources management and use. Uniqueness of the Georgian cultivated grapevine gene pool together with its close relatedness with the wild compartment makes this country a good candidate to address questions regarding domestication and grapevine genetic resource conservation. 相似文献
84.
Antonio?MasettiEmail authorView authors OrcID profile Serena?Magagnoli Francesco?Lami Alberto?Lanzoni Giovanni?Burgio 《BioControl》2018,63(5):665-675
Since the mid-2000s, the exotic coccinellid species Harmonia axyridis (Pallas) has established itself in Northern Italy, raising serious concerns about possible repercussions on native ladybirds. In this study we compared the ladybird assemblages in 2015–2016 with those sampled in 1995–1996, before the arrival of H. axyridis. Surveys were carried out in the same sites and with the same methods for both periods. Aphidophagous ladybirds were sampled in hedgerows and herbaceous habitats at field margins by mechanical knockdown and sweeping net, respectively. The changes in the structure of ladybird communities after the arrival of H. axyridis were significantly different between arboreal and herbaceous habitats. Harmonia axyridis is currently the dominant species in shrubs and trees, and all the native ladybird species taken together account for only approximately one third of the total individuals sampled in 2015–2016. On the other hand, the relative abundance of the exotic species in herbaceous habitats was low, and it has had a negligible relevance on the structure of ladybird communities on grasslands. Among native species, Adalia bipunctata (L.), whose ecological niche largely overlaps with that of H. axyridis, suffered the largest decline between 1995–1996 and 2015–2016. The co-occurrence of H. axyridis invasion and the regression of A. bipunctata suggest a direct impact of the exotic species, because no other major modifications occurred in the studied areas between sampling periods. 相似文献
85.
Massimo Nepi Massimo Guarnieri Serena Mugnaini Laura Cresti Ettore Pacini Corresp. Author Beti Piotto 《Grana》2013,52(3):148-151
Pollen viability of Juniperus communis L. and other gymnosperms with taxoid type pollen cannot be assessed with the more common viability tests because the thick sporoderm prevents reagents from penetrating into the cytoplasm. Here we describe a technique for pre‐hydration of pollen that overcomes this problem so that the common FCR test can be used to assess its viability. Pollen of J. communis must be re‐hydrated by suspending in water. This re‐hydration causes the splitting of the exine and a huge swelling of the intine. The sporoderm becomes permeable to fluoresceine diacetate and the FCR‐viability test can be applied. The FCR result is supported by scoring the germination percentage in vitro. 相似文献
86.
Aminoglycoside binding to the HIV-1 RNA dimerization initiation site: thermodynamics and effect on the kissing-loop to duplex conversion 总被引:2,自引:1,他引:2 下载免费PDF全文
Bernacchi S Freisz S Maechling C Spiess B Marquet R Dumas P Ennifar E 《Nucleic acids research》2007,35(21):7128-7139
Owing to a striking, and most likely fortuitous, structural and sequence similarity with the bacterial 16 S ribosomal A site, the RNA kissing-loop complex formed by the HIV-1 genomic RNA dimerization initiation site (DIS) specifically binds 4,5-disubstituted 2-deoxystreptamine (2-DOS) aminoglycoside antibiotics. We used chemical probing, molecular modeling, isothermal titration calorimetry (ITC) and UV melting to investigate aminoglycoside binding to the DIS loop–loop complex. We showed that apramycin, an aminoglycoside containing a bicyclic moiety, also binds the DIS, but in a different way than 4,5-disubstituted 2-DOS aminoglycosides. The determination of thermodynamic parameters for various aminoglycosides revealed the role of the different rings in the drug–RNA interaction. Surprisingly, we found that the affinity of lividomycin and neomycin for the DIS (Kd ~ 30 nM) is significantly higher than that obtained in the same experimental conditions for their natural target, the bacterial A site (Kd ~ 1.6 µM). In good agreement with their respective affinity, aminoglycoside increase the melting temperature of the loop–loop interaction and also block the conversion from kissing-loop complex to extended duplex. Taken together, our data might be useful for selecting new molecules with improved specificity and affinity toward the HIV-1 DIS RNA. 相似文献
87.
Matteo Brunelli Serena Beccari Romano Colombari Stefano Gobbo Luca Giobelli Andrea Pellegrini Marco Chilosi Maria Lunardi Guido Martignoni Aldo Scarpa Albino Eccher 《Diagnostic pathology》2014,9(Z1):S12
Background
Validation of digital whole slide images is crucial to ensure that diagnostic performance is at least equivalent to that of glass slides and light microscopy. The College of American Pathologists Pathology and Laboratory Quality Center recently developed recommendations for internal digital pathology system validation. Following these guidelines we sought to validate the performance of a digital approach for routine diagnosis by using an iPad and digital control widescreen-assisted workstation through a pilot study.Methods
From January 2014, 61 histopathological slides were scanned by ScanScope Digital Slides Scanner (Aperio, Vista, CA). Two independent pathologists performed diagnosis on virtual slides in front of a widescreen by using two computer devices (ImageScope viewing software) located to different Health Institutions (AOUI Verona) connected by local network and a remote image server using an iPad tablet (Aperio, Vista, CA), after uploading the Citrix receiver for iPad. Quality indicators related to image characters and work-flow of the e-health cockpit enterprise system were scored based on subjective (high vs poor) perception. The images were re-evaluated two weeks apart.Results
The whole glass slides encountered 10 liver: hepatocarcinoma, 10 renal carcinoma, 10 gastric carcinoma and 10 prostate biopsies: adenocarcinoma, 5 excisional skin biopsies: melanoma, 5 lymph-nodes: lymphoma. 6 immuno- and 5 special stains were available for intra- and internet remote viewing. Scan times averaged two minutes and 54 seconds per slide (standard deviation 2 minutes 34 seconds). Megabytes ranged from 256 to 680 (mean 390) per slide storage. Reliance on glass slide, image quality (resolution and color fidelity), slide navigation time, simultaneous viewers in geographically remote locations were considered of high performance score. Side by side comparisons between diagnosis performed on tissue glass slides versus widescreen were excellent showing an almost perfect concordance (0.81, kappa index).Conclusions
We validated our institutional digital pathology system for routine diagnostic facing with whole slide images in a cockpit enterprise digital system or iPad tablet. Computer widescreens are better for diagnosing scanned glass slide that iPad. For urgent requests, iPad may be used. Legal aspects have to be soon faced with to permit the clinical use of this technology in a manner that does not compromise patient care.88.
Gavazzo P Vella S Marchetti C Nizzari M Cancedda R Pagano A 《Journal of neurochemistry》2011,119(5):989-1001
Neuroblastoma is a pediatric cancer characterized by high malignancy and remarkable cell heterogeneity within the tumor nodules. It has been previously shown that the over-expression of a specific non-coding RNA, NDM29, reduces neuroblastoma development promoting cell differentiation. We have used neuroblastoma cells expressing NDM29 at its basal level (Mock cells) or at 5.4-fold higher levels (S1 cells) to investigate whether a functional differentiation correlates with morphological and biochemical development induced by NDM29 expression. First, analyzing the expression of specific markers we demonstrated that NDM29 expression is accompanied by a well coordinated differentiation process toward a neuron-like, rather than toward a glial-like, phenotype. Next, we defined the neuron-like traits of S1 in terms of secretion of cytokines involved in axon guidance, synapse formation and neurite outgrowth. Finally, we characterized the ionic channel apparatus of S1 cells by patch-clamp technique and compared with the Mock counterpart. S1 cells showed much higher levels of fast inactivating Na(+) current and were able to generate mature action potentials. Moreover, they developed expression of functional GABA(A) receptors on their membrane. In contrast, the two cell lines shared very similar pools of functional K(+) channels, although slight quantitative differences can be described. Our results suggest that a maturation occurs in neuroblastoma as a consequence of NDM29 expression, inducing the appearance of neuronal-like properties. In this context, S1 cells may represent a novel in vitro tool for electrophysiological and pharmacological studies of human cells of the neural lineage. 相似文献
89.
Raffi Tonikian Xiaofeng Xin Christopher P. Toret David Gfeller Christiane Landgraf Simona Panni Serena Paoluzi Luisa Castagnoli Bridget Currell Somasekar Seshagiri Haiyuan Yu Barbara Winsor Marc Vidal Mark B. Gerstein Gary D. Bader Rudolf Volkmer Gianni Cesareni David G. Drubin Philip M. Kim Sachdev S. Sidhu Charles Boone 《PLoS biology》2009,7(10)
SH3 domains are peptide recognition modules that mediate the assembly of diverse biological complexes. We scanned billions of phage-displayed peptides to map the binding specificities of the SH3 domain family in the budding yeast, Saccharomyces cerevisiae. Although most of the SH3 domains fall into the canonical classes I and II, each domain utilizes distinct features of its cognate ligands to achieve binding selectivity. Furthermore, we uncovered several SH3 domains with specificity profiles that clearly deviate from the two canonical classes. In conjunction with phage display, we used yeast two-hybrid and peptide array screening to independently identify SH3 domain binding partners. The results from the three complementary techniques were integrated using a Bayesian algorithm to generate a high-confidence yeast SH3 domain interaction map. The interaction map was enriched for proteins involved in endocytosis, revealing a set of SH3-mediated interactions that underlie formation of protein complexes essential to this biological pathway. We used the SH3 domain interaction network to predict the dynamic localization of several previously uncharacterized endocytic proteins, and our analysis suggests a novel role for the SH3 domains of Lsb3p and Lsb4p as hubs that recruit and assemble several endocytic complexes. 相似文献
90.
Deletion of PsbM in tobacco alters the QB site properties and the electron flow within photosystem II 总被引:1,自引:0,他引:1
Umate P Schwenkert S Karbat I Dal Bosco C Mlcòchová L Volz S Zer H Herrmann RG Ohad I Meurer J 《The Journal of biological chemistry》2007,282(13):9758-9767
Photosystem II, the oxygen-evolving complex of photosynthetic organisms, includes an intriguingly large number of low molecular weight polypeptides, including PsbM. Here we describe the first knock-out of psbM using a transplastomic, reverse genetics approach in a higher plant. Homoplastomic Delta psbM plants exhibit photoautotrophic growth. Biochemical, biophysical, and immunological analyses demonstrate that PsbM is not required for biogenesis of higher order photosystem II complexes. However, photosystem II is highly light-sensitive, and its activity is significantly decreased in Delta psbM, whereas kinetics of plastid protein synthesis, reassembly of photosystem II, and recovery of its activity are comparable with the wild type. Unlike wild type, phosphorylation of the reaction center proteins D1 and D2 is severely reduced, whereas the redox-controlled phosphorylation of photosystem II light-harvesting complex is reversely regulated in Delta psbM plants because of accumulation of reduced plastoquinone in the dark and a limited photosystem II-mediated electron transport in the light. Charge recombination in Delta psbM measured by thermoluminescence oscillations significantly differs from the 2/6 patterns in the wild type. A simulation program of thermoluminescence oscillations indicates a higher Q(B)/Q(-)(B) ratio in dark-adapted mutant thylakoids relative to the wild type. The interaction of the Q(A)/Q(B) sites estimated by shifts in the maximal thermoluminescence emission temperature of the Q band, induced by binding of different herbicides to the Q(B) site, is changed indicating alteration of the activation energy for back electron flow. We conclude that PsbM is primarily involved in the interaction of the redox components important for the electron flow within, outward, and backward to photosystem II. 相似文献