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31.
Hoggart CJ Chadeau-Hyam M Clark TG Lampariello R Whittaker JC De Iorio M Balding DJ 《Genetics》2007,177(3):1725-1731
Simulation is an invaluable tool for investigating the effects of various population genetics modeling assumptions on resulting patterns of genetic diversity, and for assessing the performance of statistical techniques, for example those designed to detect and measure the genomic effects of selection. It is also used to investigate the effectiveness of various design options for genetic association studies. Backward-in-time simulation methods are computationally efficient and have become widely used since their introduction in the 1980s. The forward-in-time approach has substantial advantages in terms of accuracy and modeling flexibility, but at greater computational cost. We have developed flexible and efficient simulation software and a rescaling technique to aid computational efficiency that together allow the simulation of sequence-level data over large genomic regions in entire diploid populations under various scenarios for demography, mutation, selection, and recombination, the latter including hotspots and gene conversion. Our forward evolution of genomic regions (FREGENE) software is freely available from www.ebi.ac.uk/projects/BARGEN together with an ancillary program to generate phenotype labels, either binary or quantitative. In this article we discuss limitations of coalescent-based simulation, introduce the rescaling technique that makes large-scale forward-in-time simulation feasible, and demonstrate the utility of various features of FREGENE, many not previously available. 相似文献
32.
Lepori MB Lovicu M Dessi V Zappu A Incollu S Zancan L Giacchino R Iorio R Vajro P Maggiore G Marcellini M Barbera C Pellecchia MT Simonetti R Kostic V Farci AM Solinas A De Virgiliis S Cao A Loudianos G 《Genetic testing》2007,11(3):328-332
Herein we report the results of mutation analysis of the ATP7B gene in a group of 134 Wilson disease (WD) families (268 chromosomes) prevalently of Italian origin. Using the SSCP and sequencing methods we identified 71 disease-causing mutations. Twenty-four were novel, while 19 more mutations already described, were identified in new populations in this study. A known mutation G591D showed a regional distribution, since it was only detected in 38.5% of the analyzed chromosomes in WD patients originating from Apulia, a region of South Italy. Detection of new mutations in the ATP7B gene increases our capability of molecular analysis that is essential for early diagnosis and treatment of WD. 相似文献
33.
Differential detection of potentially hazardous Fusarium species in wheat grains by an electronic nose 总被引:1,自引:0,他引:1
Fungal infestation on wheat is an increasingly grave nutritional problem in many countries worldwide. Fusarium species are especially harmful pathogens due to their toxic metabolites. In this work we studied volatile compounds released by F. cerealis, F. graminearum, F. culmorum and F. redolens using SPME-GC/MS. By using an electronic nose we were able to differentiate between infected and non-infected wheat grains in the post-harvest chain. Our electronic nose was capable of distinguishing between four wheat Fusaria species with an accuracy higher than 80%. 相似文献
34.
The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus mediates attachment to sialic acid receptors, as well as cleavage of the same moiety. HN also interacts with the other viral glycoprotein, the fusion (F) protein, to promote membrane fusion. The ectodomain of the HN spike consists of a stalk and a terminal globular head. The most conserved part of the stalk consists of two heptad repeats separated by a nonhelical intervening region (residues 89 to 95). Several amino acid substitutions for a completely conserved proline residue in this region not only impair fusion and the HN-F interaction but also decrease neuraminidase activity in the globular domain, suggesting that the substitutions may alter HN structure. Substitutions for L94 also interfere with fusion and the HN-F interaction but have no significant effect on any other HN function. Amino acid substitutions at other positions in the intervening region also modulate only fusion. In all cases, diminished fusion correlates with a decreased ability of the mutated HN protein to interact with F at the cell surface. These findings indicate that the intervening region is critical to the role of HN in the promotion of fusion and may be directly involved in its interaction with the homologous F protein. 相似文献
35.
Mechanism of CD150 (SLAM) down regulation from the host cell surface by measles virus hemagglutinin protein
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Measles virus has been reported to enter host cells via either of two cellular receptors, CD46 and CD150 (SLAM). CD46 is found on most cells of higher primates, while SLAM is expressed on activated B, T, and dendritic cells and is an important regulatory molecule of the immune system. Previous reports have shown that measles virus can down regulate expression of its two cellular receptors on the host cell surface during infection. In this study, the process of down regulation of SLAM by measles virus was investigated. We demonstrated that expression of the hemagglutinin (H) protein of measles virus was sufficient for down regulation. Our studies provided evidence that interactions between H and SLAM in the endoplasmic reticulum (ER) can promote the down regulation of SLAM but not CD46. In addition, we demonstrated that interactions between H and SLAM at the host cell surface can also contribute to SLAM down regulation. These results indicate that two mechanisms involving either intracellular interactions between H and SLAM in the ER or receptor-mediated binding to H at the surfaces of host cells can lead to the down regulation of SLAM during measles virus infection. 相似文献
36.
F. Pilato P. Profice F. Ranieri F. Capone R. Di Iorio L. Florio V. Di Lazzaro 《Molecular neurobiology》2012,46(3):563-571
Several studies demonstrated in experimental models and in humans synaptic plasticity impairment in some neurodegenerative and neuropsychiatric diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and schizophrenia. Recently new neurophysiological tools, such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation, have been introduced in experimental and clinical settings for studying physiology of the brain and modulating cortical activity. These techniques use noninvasive transcranial electrical or magnetic stimulation to modulate neurons activity in the human brain. Cortical stimulation might enhance or inhibit the activity of cortico?Csubcortical networks, depending on stimulus frequency and intensity, current polarity, and other stimulation parameters such as the configuration of the induced electric field and stimulation protocols. On this basis, in the last two decades, these techniques have rapidly become valuable tools to investigate physiology of the human brain and have been applied to treat drug-resistant neurological and psychiatric diseases. Here we describe these techniques and discuss the mechanisms that may explain these effects. 相似文献
37.
Vanan I Dong Z Tosti E Warshaw G Symons M Ruggieri R 《Cellular and molecular neurobiology》2012,32(7):1199-1208
Ionizing radiation (IR) induces a DNA damage response that includes activation of cell cycle checkpoints, leading to cell cycle arrest. In addition, IR enhances cell invasiveness of glioblastoma cells, among other tumor cell types. Using RNA interference, we found that the protein kinase MRK, previously implicated in the DNA damage response to IR, also inhibits IR-induced cell migration and invasion of glioblastoma cells. We showed that MRK activation by IR requires the checkpoint protein Nbs1 and that Nbs1 is also required for IR-stimulated migration. In addition, we show that MRK acts upstream of Chk2 and that Chk2 is also required for IR-stimulated migration and invasion. Thus, we have identified Nbs1, MRK, and Chk2 as elements of a novel signaling pathway that mediates IR-stimulated cell migration and invasion. Interestingly, we found that inhibition of cell cycle progression, either with the CDK1/2 inhibitor CGP74514A or by downregulation of the CDC25A protein phosphatase, restores IR-induced migration and invasion in cells depleted of MRK or Chk2. These data indicate that cell cycle progression, at least in the context of IR, exerts a negative control on the invasive properties of glioblastoma cells and that checkpoint proteins mediate IR-induced invasive behavior by controlling cell cycle arrest. 相似文献
38.
39.
Pagliarani G Paris R Iorio AR Tartarini S Del Duca S Arens P Peters S van de Weg E 《Molecular breeding : new strategies in plant improvement》2012,29(3):759-778
European populations exhibit progressive sensitisation to food allergens, and apples are one of the foods for which sensitisation
is observed most frequently. Apple cultivars vary greatly in their allergenic characteristics, and a better understanding
of the genetic basis of low allergenicity may therefore allow allergic individuals to increase their fruit intake. Mal d 1
is considered to be a major apple allergen, and this protein is encoded by the most complex allergen gene family. Not all
Mal d 1 members are likely to be involved in allergenicity. Therefore, additional knowledge about the existence and characteristics
of the different Mal d 1 genes is required. In the present study, we investigated the genomic organisation of the Mal d 1 gene cluster in linkage group 16 of apple through the sequencing of two bacterial artificial chromosome clones. The results
provided new information on the composition of this family with respect to the number and orientation of functional and pseudogenes
and their physical distances. The results were compared with the apple and peach genome sequences that have recently been
made available. A broad analysis of the whole apple genome revealed the presence of new genes in this family, and a complete
list of the observed Mal d 1 genes is supplied. Thus, this study provides an important contribution towards a better understanding of the genetics of
the Mal d 1 family and establishes the basis for further research on allelic diversity among cultivars in relation to variation in allergenicity. 相似文献
40.
Donato Traversa Annunziata Giangaspero Umberto Molini Raffaella Iorio Barbara Paoletti Domenico Otranto Carla Giansante 《Applied microbiology》2004,70(7):4367-4370
Chamelea gallina clams collected from the mouths of rivers along the Adriatic Sea (central Italy) were found to harbor Cryptosporidium parvum (genotype 2), which is the lineage involved in zoonotic transmission. The clams were collected from the mouths of rivers near whose banks ruminants are brought to graze. This paper reports the environmental spread of C. parvum in Italy and highlights the fact that genotyping of seaborne Cryptosporidium isolates is a powerful tool with which to investigate the transmission patterns and epidemiology of this microorganism. 相似文献