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461.

Background  

Attenuation of the EGFR (Epidermal Growth Factor Receptor) signalling cascade is crucial to control cell fate during development. A candidate-based RNAi approach in C. elegans identified CDT-2 as an attenuator of LET-23 (EGFR) signalling. Human CDT2 is a component of the conserved CDT2/CUL4/DDB1 ubiquitin ligase complex that plays a critical role in DNA replication and G2/M checkpoint. Within this complex, CDT2 is responsible for substrate recognition. This ubiquitin ligase complex has been shown in various organisms, including C. elegans, to target the replication-licensing factor CDT1, and the CDK inhibitor p21. However, no previous link to EGFR signalling has been identified.  相似文献   
462.
463.
The objective of this study was to determine whether MVV can be transmitted by ovine embryos produced in vitro and whether the zona pellucida (ZP) provides any protection against MVV infection.Zona pellucida (ZP)-intact and ZP-free embryos, produced in vitro, at the 8-16 cell stage, were cocultured for 72h in an insert over an ovine oviduct epithelial cell (OOEC)-goat synovial membrane (GSM) cell monolayer that had been previously infected with MVV (K1514 strain). The embryos were then washed and transferred to either direct contact or an insert over a fresh GSM cell monolayer for 6 h. The presence of MVV was detected using RT-PCR on the ten washing fluids and by the observation of typical cytopathic effects (CPE) in the GSM cell monolayer, which was cultured for 6 weeks.This experiment was repeated 4 times with the same results: MVV viral RNA was detected using RT-PCR in the first three washing media, while subsequent baths were always negative. Specific cytopathic effects of MVV infection and MVV-proviral DNA were detected in GSM cells that were used as a viral indicator and cocultured in direct contact or as an insert with MVV-exposed ZP-free embryos. However, no signs of MVV infection were detected in cells that were cocultured with exposed ZP-intact or non-exposed embryos.This study clearly demonstrates that (i) in vitro, ZP-free, early ovine embryos, which had been exposed to 103 TCID50/m MVV in vitro, are capable of transmitting the virus to susceptible GSM target cells, and that (ii) the IETS recommendations for handling in vivo produced bovine embryos (use of ZP-intact embryos without adherent material and performing ten washes) are effective for the elimination of in vitro MVV infection from in vitro produced ovine embryos. The absence of interaction between ZP-intact embryos and MVV suggests that the in vitro produced embryo zona pellucida provides an effective protective barrier.  相似文献   
464.
S Moir  J Perreault    L Poulin 《Journal of virology》1996,70(11):8019-8028
Evidence from both structural and functional studies of the CD4 molecule suggests that several domains, including the transmembrane (TM) domain and the adjoining extracellular region (D4-TM linker), contribute to the post-gp12O-binding events leading to human immunodeficiency virus-mediated membrane fusion. To investigate such a role in syncytium formation and cell-free infectivity, we generated several deletion and substitution mutations in the TM and D4-TM linker regions of the CD4 molecule. We found that while the TM domain of CD4 was dispensable for cell-cell and virus-cell interactions, modifications in the D4-TM linker led to perturbations in both processes. Deletion of the five amino acid residues linking D4 to the TM domain resulted in a delayed and reduced capacity to form syncytia, whereas replacement of the residues with the heterologous sequence from the CD8 molecule restored the kinetic profile to wild-type CD4 levels. On the other hand, both mutants of the CD4 D4-TM linker demonstrated delayed cell-free human immunodeficiency virus type 1 infectivity profiles. The defective fusion capacity may be linked to structural perturbations identified with anti-CD4 monoclonal antibodies in the D1-D2 interface and D3 domain of the deletion mutant yet absent in D1 and D4. While all cells were found to bind comparable levels of gp120, both D4-TM linker mutants appeared to induce a decrease in the V3 loop exposure of bound gp120. This underexposure may explain the delays in cell-free infectivities observed for both of these mutants. Together, these findings confirm a role for regions of the CD4 molecule located outside D1 in post-gp120-binding events and suggest that the D4-TM interface contributes to the conformational changes that direct the fusion process.  相似文献   
465.
As the number of non-synonymous single nucleotide polymorphisms (nsSNPs) identified through whole-exome/whole-genome sequencing programs increases, researchers and clinicians are becoming increasingly reliant upon computational prediction algorithms designed to prioritize potential functional variants for further study. A large proportion of existing prediction algorithms are ‘disease agnostic’ but are nevertheless quite capable of predicting when a mutation is likely to be deleterious. However, most clinical and research applications of these algorithms relate to specific diseases and would therefore benefit from an approach that discriminates between functional variants specifically related to that disease from those which are not. In a whole-exome/whole-genome sequencing context, such an approach could substantially reduce the number of false positive candidate mutations. Here, we test this postulate by incorporating a disease-specific weighting scheme into the Functional Analysis through Hidden Markov Models (FATHMM) algorithm. When compared to traditional prediction algorithms, we observed an overall reduction in the number of false positives identified using a disease-specific approach to functional prediction across 17 distinct disease concepts/categories. Our results illustrate the potential benefits of making disease-specific predictions when prioritizing candidate variants in relation to specific diseases. A web-based implementation of our algorithm is available at http://fathmm.biocompute.org.uk.  相似文献   
466.
The past few years have seen a noticeable increase in the emergence of infectious diseases in wildlife, especially vector-borne diseases, presenting a challenge for the conservation of endangered species. One such vector-borne disease, avian malaria (Plasmodium spp.) is on the rise in New Zealand avifauna, threatening bird populations that are among the most extinction-prone in the world. Furthermore, recent reports have outlined an increase in deaths of native iconic bird species specifically due to this disease. In order to help manage breakouts of this pathogen at a local scale, we need a better understanding of potential drivers of the emergence of avian malaria in wild New Zealand avifauna. Here, we set to test the role of climatic drivers in synchronizing contacts between avian hosts and vectors, assess the temporal stability of transmission dynamics between years, and determine the role of introduced species in causing spill-over of this pathogen towards native species. Our study focused on three sites that were sampled regularly during two consecutive years in the austral summer, each site being adjacent to a breeding colony of Yellow-eyed penguins (Megadyptes antipodes). Our results reveal an overall temporal stability of avian malaria incidence patterns, with a decrease in infection throughout the austral summer for both sampled years. Moreover, we highlight a phylogenetic signal among sampled bird species, with introduced species being more heavily infected by avian malaria than their native counterparts. In contrast, we found no effect of the two climatic drivers investigated, temperature and rainfall, on mosquito abundance. Our results suggest a strong effect of alien species acting as reservoirs for diseases spilling-over towards immunologically naïve species, and provide conservation managers with a critical timeframe to control avian malaria breakouts.  相似文献   
467.
Wetlands Ecology and Management - The Domaine de la Palissade is a 700-ha nature reserve located at the mouth of the Rhône river in southern France. Since 2006, the tidal wetlands have been...  相似文献   
468.
Deep‐sea octopuses of the genus Muusoctopus are thought to have originated in the Pacific Northern Hemisphere and then diversified throughout the Pacific and into the rest of the World Ocean. However, this hypothesis was inferred only from molecular divergence times. Here, the ancestral distribution and dispersal routes are estimated by Bayesian analysis based on a new phylogeny including 38 specimens from the south‐eastern Pacific Ocean. Morphological data and molecular sequences of three mitochondrial genes (16S rRNA, COI and COIII) are presented. The morphological data confirm that specimens newly acquired from off the coast of Chile comprise two species: Muusoctopus longibrachus and the poorly described species, Muusoctopus eicomar. The latter is here redescribed and is clearly distinguished from M. longibrachus and other closely related species in the region. A gene tree was built using Bayesian analysis to infer the phylogenetic position of these species within the species group, revealing that a large genetic distance separates the two sympatric Chilean species. M. longibrachus is confirmed as the sister species of Muusooctopus eureka from the Falkland Islands; while M. eicomar is a sister species of Muusoctopus yaquinae from the North Pacific, most closely related to the amphi‐Atlantic species Muusoctopus januarii. Molecular divergence times and ancestral distribution analyses suggest that genus Muusoctopus may have originated in the North Atlantic: one lineage dispersed directly southward to the Magellan region and another dispersed southward along the Eastern Pacific to the Southern Ocean and Antarctica. The Muusoctopus species in the Southern Hemisphere have different phylogenetic origins and represent independent invasions of this region.  相似文献   
469.
Manipulation of host phenotype by parasites can require a collective effort from many individuals. The cost of manipulation may only be paid by the individuals actually inducing the manipulation, while its benefits are reaped by all. Here, we determine if there is genetic variation in manipulative effort among different clonal lineages of the trematode Curtuteria australis, and whether the decision to manipulate is context‐dependent. C. australis impairs the burrowing efficiency of its second intermediate host, the cockle Austrovenus stutchburyi, by encysting at the tip of the cockle's foot, which facilitates the parasite's trophic transmission to shorebirds. However, manipulative individuals at the tip of the foot are vulnerable to non‐host predators (foot‐cropping fish); in contrast, those encysted at the base of the foot, although they do not contribute to manipulation, are safe from foot‐croppers and can benefit from altered host phenotype. In an experimental study, different clonal lineages showed no significant variation in their tendency to encyst in the tip versus the base of the foot, with only the former contributing to host manipulation. However, the decision to manipulate was intensity‐dependent: the greater the number of parasites already committed to manipulation (i.e. already encysted in the foot tip), the more likely newly arriving parasites were to join them. These findings indicate considerable intraspecific variation in the strategies adopted by ‘manipulator’ parasites, with external influences determining what a parasite actually does.  相似文献   
470.
Density, body mass and parasite species richness of terrestrial mammals   总被引:9,自引:0,他引:9  
We investigated the relationships between helminth species richness and body mass and density of terrestrial mammals. Cross-species analysis and the phylogenetically independent contrast method produced different results. A non-phylogenetic approach (cross-species comparisons) led to the conclusion that parasite richness is linked to host body size. However, an analysis using phylogenetically independent contrasts showed no relationship between host body size and parasite richness. Conversely, a non-phylogenetic approach generated a negative relationship between parasite richness and host density, whereas the independent contrast method showed the opposite trend – that is, parasite richness is positively correlated with host density. From an evolutionary perspective, our results suggest that opportunities for parasite colonization depend more closely on how many hosts are available in a given area than on how large the hosts are. From an epidemiological point of view, our results confirm theoretical models which assume that host density is linked to the opportunity of a parasite to invade a population of hosts. Our findings also suggest that parasitism may be a cost associated with host density. Finally, we provide some support for the non-linear allometry between density and mammal body mass (Silva and Downing, 1995), and explain why host density and host body mass do not relate equally to parasite species richness.  相似文献   
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