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1.
Narayanan S  Reif B 《Biochemistry》2005,44(5):1444-1452
Alzheimer's disease (AD) is characterized by the accumulation of insoluble fibrillar aggregates of beta-amyloid peptides (Abeta), a 39-42 residue peptide, in the brain of AD patients. It is hypothesized that the disease causing form is not the fibrillar species but an oligomeric Abeta molecule, which is often referred to as the "critical oligomer" of Abeta. We show in this paper that Abeta(1-40) undergoes chemical exchange between a monomeric, soluble state and an oligomeric, aggregated state under physiological conditions. In circular dichroism spectroscopy, we observe for this intermediate an alpha-helical structure. The oligomer is assigned a molecular weight of >100 kDa by diffusion-ordered spectroscopy-solution-state NMR spectroscopy (NMR). We can show by saturation transfer difference NMR experiments that the oligomer is related to monomeric Abeta. This experiment also allows us to identify the chemical groups that are involved in interactions between mono- and oligomeric Abeta molecules. Variation of the anionic strength in the buffer induces a shift of equilibrium between mono- and oligomeric states and possibly allows for the stabilization of these intermediate structures.  相似文献   
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3.
Maize (Zea mays L.) breeders are concerned about the narrowing of the genetic base of elite germplasm. To reverse this trend, elite germplasm from other geographic regions can be introgressed, but due to lack of adaptation it is difficult to assess their breeding potential in the targeted environment. The objectives of this study were to (1) investigate the relationship between European and US maize germplasm, (2) examine the suitability of different mega-environments and measures of performance to assess the breeding potential of exotics, and (3) study the relationship of genetic distance with mid-parent heterosis (MPH). Eight European inbreds from the Dent and Flint heterotic groups, 11 US inbreds belonging to Stiff Stalk (SS), non-Stiff Stalk (NSS), and CIMMYT Pool 41, and their 88 factorial crosses in F1 and F2 generations were evaluated for grain yield and dry matter concentration. The experiments were conducted in three mega-environments: Central Europe (target mega-environment), US Cornbelt (mega-environment where donor lines were developed), and Southeast Europe (an intermediate mega-environment). The inbreds were also fingerprinted with 266 SSR markers. Suitable criteria to identify promising exotic germplasm were F1 hybrid performance in the targeted mega-environment and F1 and parental performance in the intermediate mega-environment. Marker-based genetic distances reflected relatedness among the inbreds, but showed no association with MPH. Based on genetic distance, MPH, and F1 performance, we suggest to introgress SS germplasm into European Dents and NSS into European Flints, in order to exploit the specific adaptation of European flint germplasm and the excellent combining ability of US germplasm in European maize breeding programs.  相似文献   
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Background  

Chromosomal painting, using whole chromosome probes from humans and Saguinus oedipus, was used to establish karyotypic divergence among species of the genus Cebus, including C. olivaceus, C. albifrons, C. apella robustus and C. apella paraguayanus. Cytogenetic studies suggested that the species of this genus have conservative karyotypes, with diploid numbers ranging from 2n = 52 to 2n = 54.  相似文献   
5.
Bottlenose dolphins (Tursiops truncatus) from estuarine waters of Indian River Lagoon, FL (IRL) and Charleston, SC (CHS) were cultured to screen for microorganism colonization and to assess antibiotic sensitivity. Swabs (n = 909) were collected from the blowhole, gastric fluid, and feces of 171 individual dolphins The most frequently cultured organisms were Plesiomonas shigelloides (n = 161), Aeromonas hydrophila (n = 144), Escherichia coli (n = 85), and Pseudomonas fluorescens (n = 82). In descending frequency, organisms demonstrated resistance to erythromycin, ampicillin, and cephalothin. Human and animal pathogens resistant to antibiotics used in human and veterinary medicine were cultured. Escherichia coli (E. coli) more often was resistant in IRL dolphins. Three cases of methicillin-resistant Staphylococcus aureus (MRSA) were found at CHS. Emergence of antibiotic resistance is not confined to humans. Bottlenose dolphins may serve as sentinels for transfer of resistance from humans and animals or indicate that antibiotics are reaching the marine environment and causing resistance to emerge through selective pressure and genetic adaptation.  相似文献   
6.
T and B lymphocytes migrate hundreds of micrometers each day to survey the body's lymphoid tissues for antigens. No other mammalian cell type undergoes such extensive and continual movement, raising the question of whether lymphocytes have specializations to support their migratory behavior. This possibility has recently gained support from studies of mice deficient in DOCK2, a member of the Caenorhabditis elegans Ced-5, mammalian DOCK180 and Drosophila melanogaster myoblast city (CDM) family of scaffolding proteins. Migration of lymphocytes, but not other cell types, is severely disrupted in DOCK2-deficient mice. Despite the conserved role of CDM molecules in regulating Rac activation and actin assembly, relatively little is known about how these molecules function. Here, we review the role of DOCK2 in lymphocyte homing to lymphoid tissues and discuss recent findings for other CDM family molecules that provide a basis for understanding how DOCK2 might function in lymphocytes.  相似文献   
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8.
The antibody light chain (LC) consists of two domains and is essential for antigen binding in mature immunoglobulins. The two domains are connected by a highly conserved linker that comprises the structurally important Arg108 residue. In antibody light chain (AL) amyloidosis, a severe protein amyloid disease, the LC and its N-terminal variable domain (VL) convert to fibrils deposited in the tissues causing organ failure. Understanding the factors shaping the architecture of the LC is important for basic science, biotechnology and for deciphering the principles that lead to fibril formation. In this study, we examined the structure and properties of LC variants with a mutated or extended linker. We show that under destabilizing conditions, the linker modulates the amyloidogenicity of the LC. The fibril formation propensity of LC linker variants and their susceptibility to proteolysis directly correlate implying an interplay between the two LC domains. Using NMR and residual dipolar coupling-based simulations, we found that the linker residue Arg108 is a key factor regulating the relative orientation of the VL and CL domains, keeping them in a bent and dense, but still flexible conformation. Thus, inter-domain contacts and the relative orientation of VL and CL to each other are of major importance for maintaining the structural integrity of the full-length LC.  相似文献   
9.

Background

The main goal of our study was to investigate the implementation, prospects, and limits of marker imputation for quantitative genetic studies contrasting map-independent and map-dependent algorithms. We used a diversity panel consisting of 372 European elite wheat (Triticum aestivum L.) varieties, which had been genotyped with SNP arrays, and performed intensive simulation studies.

Results

Our results clearly showed that imputation accuracy was substantially higher for map-dependent compared to map-independent methods. The accuracy of marker imputation depended strongly on the linkage disequilibrium between the markers in the reference panel and the markers to be imputed. For the decay of linkage disequilibrium present in European wheat, we concluded that around 45,000 markers are needed for low cost, low-density marker profiling. This will facilitate high imputation accuracy, also for rare alleles. Genomic selection and diversity studies profited only marginally from imputing missing values. In contrast, the power of association mapping increased substantially when missing values were imputed.

Conclusions

Imputing missing values is especially of interest for an economic implementation of association mapping in breeding populations.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1366-y) contains supplementary material, which is available to authorized users.  相似文献   
10.
There has been increasing contact between mountain gorillas (Gorilla gorilla beringei) and the human population surrounding Bwindi Impenetrable Forest National Park (BIFNP) in Uganda. Due to the close taxonomic relationship between humans and gorillas there is potential for disease transmission between them. Preventing the introduction or spread of transmissible diseases to the gorillas is essential to protect them. We interviewed 301 villagers living in close proximity to BIFNP with a medical questionnaire in July, 2000. We collected information on demographics, vaccination and health history, and human/gorilla interaction. Our objectives were to estimate the prevalence of several diseases in the human population and to evaluate the risk of anthropozoonotic transmission from humans to gorillas. We found a high prevalence of disease symptoms such as coughing (72.1%) and fever (56.1%) compatible with acute infectious diseases; over half of the respondents (59.1%) had a specific disease diagnosis within the 6 mo preceding the study. We compared villagers who had visual contact with gorillas in the 6 mo preceding the study (53.5%) to villagers who had no visual contact (46.5%). Men were 2.3 times more likely than women to have visual contact with gorillas. In general, the frequency of disease history and symptoms was similar for people with and without contact. The high prevalence of acute infectious diseases in the population surrounding BIFNP and the high rate of contact with gorillas creates the potential for anthropozoonotic disease transmission.  相似文献   
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