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排序方式: 共有215条查询结果,搜索用时 15 毫秒
91.
92.
Wang Z Collighan RJ Gross SR Danen EH Orend G Telci D Griffin M 《The Journal of biological chemistry》2010,285(51):40212-40229
Fibronectin (FN) deposition mediated by fibroblasts is an important process in matrix remodeling and wound healing. By monitoring the deposition of soluble biotinylated FN, we show that the stress-induced TG-FN matrix, a matrix complex of tissue transglutaminase (TG2) with its high affinity binding partner FN, can increase both exogenous and cellular FN deposition and also restore it when cell adhesion is interrupted via the presence of RGD-containing peptides. This mechanism does not require the transamidase activity of TG2 but is activated through an RGD-independent adhesion process requiring a heterocomplex of TG2 and FN and is mediated by a syndecan-4 and β1 integrin co-signaling pathway. By using α5 null cells, β1 integrin functional blocking antibody, and a α5β1 integrin targeting peptide A5-1, we demonstrate that the α5 and β1 integrins are essential for TG-FN to compensate RGD-induced loss of cell adhesion and FN deposition. The importance of syndecan-2 in this process was shown using targeting siRNAs, which abolished the compensation effect of TG-FN on the RGD-induced loss of cell adhesion, resulting in disruption of actin skeleton formation and FN deposition. Unlike syndecan-4, syndecan-2 does not interact directly with TG2 but acts as a downstream effector in regulating actin cytoskeleton organization through the ROCK pathway. We demonstrate that PKCα is likely to be the important link between syndecan-4 and syndecan-2 signaling and that TG2 is the functional component of the TG-FN heterocomplex in mediating cell adhesion via its direct interaction with heparan sulfate chains. 相似文献
93.
Lilla Römisch-Margl Gertraud Spielbauer Andre Schützenmeister Wilfried Schwab Hans-Peter Piepho Ulrich Genschel Alfons Gierl 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,120(2):369-381
Heterosis is the superior performance of hybrids over their inbred parents. Despite its importance, little is known about
the genetic and molecular basis of this phenomenon. Heterosis has been extensively exploited in plant breeding, particularly
in maize (Zea mays, L.), and is well documented in the B73 and Mo17 maize inbred lines and their F1 hybrids. In this study, we determined the
dry matter, the levels of starch and protein components and a total of 24 low-molecular weight metabolites including sugars,
sugar-phosphates, and free amino acids, in developing maize kernels between 8 and 30 days post-pollination (DPP) of the hybrid
B73 × Mo17 and its parental lines. The tissue specificity of amino acid and protein content was investigated between 16 and
30 DPP. Key observations include: (1) most of the significant differences in the investigated tissue types occurred between
Mo17 and the other two genotypes; (2) heterosis of dry matter and metabolite content was detectable from the early phase of
kernel development onwards; (3) the majority of metabolites exhibited an additive pattern. Nearly 10% of the metabolites exhibited
nonadditive effects such as overdominance, underdominance, and high-parent and low-parent dominance; (4) The metabolite composition
was remarkably dependent on kernel age, and this large developmental effect could possibly mask genotypic differences; (5)
the metabolite profiles and the heterotic patterns are specific for endosperm and embryo. Our findings illustrate the power
of metabolomics to characterize heterotic maize lines and suggest that the metabolite composition is a potential marker in
the context of heterosis research. 相似文献
94.
Marc Gerspacher Eva Altmann René Beerli Thomas Buhl Ralf Endres Rainer Gamse Jacques Kameni-Tcheudji Michaela Kneissel Karl Heinz Krawinkler Martin Missbach Alfred Schmidt Klaus Seuwen Sven Weiler Leo Widler 《Bioorganic & medicinal chemistry letters》2010,20(17):5161-5164
A series of novel benzimidazole derivatives has been designed via a scaffold morphing approach based on known calcilytics chemotypes. Subsequent lead optimisation led to the discovery of penta-substituted benzimidazoles that exhibit attractive in vitro and in vivo calcium-sensing receptor (CaSR) inhibitory profiles. In addition, synthesis and structure–activity relationship data are provided. 相似文献
95.
Seok-Hyung Kim Shu-Yu Wu Jeong-In Baek Soo Young Choi Yanhui Su Charles R. Flynn Joshua T. Gamse Kevin C. Ess Gary Hardiman Joshua H. Lipschutz Naji N. Abumrad Don C. Rockey 《PloS one》2015,10(5)
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis and fibrosis. However, the molecular pathogenesis and genetic variations causing NAFLD are poorly understood. The high prevalence and incidence of NAFLD suggests that genetic variations on a large number of genes might be involved in NAFLD. To identify genetic variants causing inherited liver disease, we used zebrafish as a model system for a large-scale mutant screen, and adopted a whole genome sequencing approach for rapid identification of mutated genes found in our screen. Here, we report on a forward genetic screen of ENU mutagenized zebrafish. From 250 F2 lines of ENU mutagenized zebrafish during post-developmental stages (5 to 8 days post fertilization), we identified 19 unique mutant zebrafish lines displaying visual evidence of hepatomegaly and/or steatosis with no developmental defects. Histological analysis of mutants revealed several specific phenotypes, including common steatosis, micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute hepatocellular necrosis. This work has identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease. 相似文献
96.
Dörr S Lechtenböhmer N Rau R Herborn G Wagner U Müller-Myhsok B Hansmann I Keyszer G 《Arthritis research & therapy》2004,6(3):R199-R207
The genetic background of rheumatoid arthritis (RA) is only partly understood, and several genes seem to be involved. The
matrix metalloproteinases MMP1 (interstitial collagenase) and MMP3 (stromelysin 1) are thought to be important in destructive joint changes seen in RA. In the present study, functional relevant
promoter polymorphisms of MMP1 and MMP3 were genotyped in 308 patients and in 110 controls, to test whether the polymorphisms contribute to the severity of the disease
measured by radiographic progression of joint destruction. For comparison, the shared epitope of HLA DR4 and DR1 (SE) was
determined by polymerase chain reaction. There was no association of MMP polymorphisms with susceptibility to RA. However,
a strong linkage disequilibrium was observed between the 1G/2G (MMP1) and the 5A/6A (MMP3) polymorphisms (P << 10-6; linkage disequilibrium index D' = 0.46). In factorial regression, the degree of radiographic joint destruction correlated significantly with the 1G-5A haplotype
(P = 0.0001) and the interaction term 'estimated number of 1G-5A haplotypes × duration of disease' (P = 0.0007). This association was phasic, indicating that possession of the 1G-5A haplotype has a protective effect over a
period of about 15 years of RA, but might be associated with a more pronounced radiographic progression later on. Similar
results were also found with the 1G allele of MMP1 alone (P = 0.015) and with the interaction term 'estimated number of 1G alleles × duration of disease' (P = 0.014). The correlation of SE with the Ratingen score was comparable (0.044). The regression model of MMP haplotypes explained 35% of the variance of the radiographic score, whereas the SE explained 29%. The 1G-5A haplotype across
the closely linked MMP1 and MMP3 gene loci is a newly described genetic factor strongly associated with the progression of joint damage in RA. Our findings
suggest that there are haplotypes in a MMP cluster region that modify the joint destruction in RA in a phasic manner. 相似文献
97.
Lena Guderjahn Andreas Gold Gertraud Stadler Caterina Gawrilow 《Attention deficit and hyperactivity disorders》2013,5(4):397-407
Children with attention deficit hyperactivity disorder (ADHD) suffer from self-regulation deficits that cause inattention, impulsivity, and hyperactivity. Self-regulation interventions may address these deficits, but to date, only few empirical studies have examined their benefits for children with ADHD in everyday life. The present study investigated three classroom interventions to promote self-regulation and tested their benefit on self-regulatory competencies (assessed with an ADHD questionnaire) in children with ADHD. Students of a special education school for children with ADHD participated in the intervention study that included three sessions (Session 1: Goal Intention or Goal Intention + If–Then Plan; Session 2: Goal Intention + If–Then Plan; Session 3: Goal Intention + If–Then Plan + Self-Monitoring). Teacher-rated self-regulatory competencies were assessed both before and after the intervention sessions. Children with ADHD had better self-regulatory competencies after their first Goal Intention + If–Then Plan Session, but lasting intervention effects were found only when children started with a mere goal intention session. 相似文献
98.
Simon-Assmann P Orend G Mammadova-Bach E Spenlé C Lefebvre O 《The International journal of developmental biology》2011,55(4-5):455-465
The interaction of endothelial cells and pericytes with their microenvironment, in particular with the basement membrane, plays a crucial role during vasculogenesis and angiogenesis. In this review, we focus on laminins, a major family of extracellular matrix molecules present in basement membranes. Laminins interact with cell surface receptors to trigger intracellular signalling that shapes cell behaviour. Each laminin exerts a distinct effect on endothelial cells and pericytes which largely depends on the adhesion receptor profile expressed on the cell surface. Moreover, proteolytic cleavage of laminins may affect their role in angiogenesis. We report in vitro and in vivo data on laminin-111, -411, -511 and -332 and their associated signalling that regulates cell behaviour and angiogenesis under normal and pathological conditions. We also discuss how tissue-specific deletion of laminin genes affects the behaviour of endothelial cells and pericytes and thus angiogenesis. Finally, we examine how coculture systems with defined laminin expression contribute to our understanding of the roles of laminins in normal and pathological vasculogenesis and angiogenesis. 相似文献
99.
100.
Disease prioritization exercises have been used by several organizations to inform surveillance and control measures. Though most methodologies for disease prioritization are based on expert opinion, it is becoming more common to include different stakeholders in the prioritization exercise. This study was performed to compare the weighting of disease criteria, and the consequent prioritization of zoonoses, by both health professionals and students in Switzerland using a Conjoint Analysis questionnaire. The health professionals comprised public health and food safety experts, cantonal physicians and cantonal veterinarians, while the student group comprised first-year veterinary and agronomy students. Eight criteria were selected for this prioritization based on expert elicitation and literature review. These criteria, described on a 3-tiered scale, were evaluated through a choice-based Conjoint Analysis questionnaire with 25 choice tasks. Questionnaire results were analyzed to obtain importance scores (for each criterion) and mean utility values (for each criterion level), and the latter were then used to rank 16 zoonoses. While the most important criterion for both groups was “Severity of the disease in humans”, the second ranked criteria by the health professionals and students were “Economy” and “Treatment in humans”, respectively. Regarding the criterion “Control and Prevention”, health professionals tended to prioritize a disease when the control and preventive measures were described to be 95% effective, while students prioritized a disease if there were almost no control and preventive measures available. Bovine Spongiform Encephalopathy was the top-ranked disease by both groups. Health professionals and students agreed on the weighting of certain criteria such as “Severity” and “Treatment of disease in humans”, but disagreed on others such as “Economy” or “Control and Prevention”. Nonetheless, the overall disease ranking lists were similar, and these may be taken into consideration when making future decisions regarding resource allocation for disease control and prevention in Switzerland. 相似文献