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71.
Simone Wahl Christina Holzapfel Zhonghao Yu Michaela Breier Ivan Kondofersky Christiane Fuchs Paula Singmann Cornelia Prehn Jerzy Adamski Harald Grallert Thomas Illig Rui Wang-Sattler Thomas Reinehr 《Metabolomics : Official journal of the Metabolomic Society》2013,9(6):1157-1167
The amount of weight loss in obese children during lifestyle intervention differs strongly between individuals. The metabolic processes underlying this variability are largely unknown. We hypothesize that metabolomics analyses of serum samples might help to identify metabolic predictors of weight loss. In this study, we investigated 80 obese children aged 6–15 years having completed the one-year lifestyle intervention program ‘Obeldicks’, 40 that achieved a substantial reduction of their body mass index standard deviation score (BMI-SDS) during this intervention (defined as BMI-SDS reduction ≥ 0.5), and 40 that did not improve their overweight status (BMI-SDS reduction < 0.1). Anthropometric and clinical parameters were measured and baseline fasting serum samples of all children were analyzed with a mass spectrometry-based metabolomics approach targeting 163 metabolites. Both univariate regression models and a multivariate least absolute shrinkage and selection operator (LASSO) approach identified lower serum concentrations of long-chain unsaturated phosphatidylcholines as well as smaller waist circumference as significant predictors of BMI-SDS reduction during intervention (p-values univariate models: 5.3E?03 to 1.0E?04). A permutation test showed that the LASSO model explained a significant part of BMI-SDS change (p = 4.6E?03). Our results suggest a role of phosphatidylcholine metabolism and abdominal obesity in body weight regulation. These findings might lead to a better understanding of the mechanisms behind the large inter-individual variation in response to lifestyle interventions, which is a prerequisite for the development of individualized intervention programs. 相似文献
72.
Several theoretical and empirical studies have examined the influence of environmental conditions on seed traits and germination strategies of annual species. A positive relationship between seed mass and dormancy has been described for annuals occupying climatically unpredictable ecosystems. Larger-seeded species tend to have higher seedling survival rates, while dormancy allows a bet-hedging strategy in unpredictable environments. Until now, these ideas have been addressed primarily for only one or a few focal species, without considering differences among populations and communities. The novelty of the present study lies in the population and community-level approach, where a comprehensive seed trait database including 158 annual species occurring along a gradient of rainfall variability and aridity in Israel was used to ask the following question: Does average seed mass and dormancy of annual populations and communities decrease with increasing aridity and rainfall unpredictability?Soil seed bank samples were collected at the end of the summer drought, before the onset of the rains, from four plant communities. Germination was tested under irrigated conditions during three consecutive germination seasons to determine the overall seed germinability in each soil sample. Seed mass was obtained from newly produced seeds collected at the study sites in late spring. The community level results showed that, in contrast to common theoretical knowledge, seed mass and dormancy of the dominant annual species decreased with increasing aridity and rainfall variability. Accordingly, a negative correlation was found between seed mass and seed germination fractions. The present study demonstrates that an analysis of seed traits along climatic gradients is significantly improved by approaches that target both population and community levels simultaneously. A critical evaluation sheds new light upon the selective pressures that act on seed ecology of annuals along a climatic gradient and facilitates formulation of more mechanistic hypotheses about factors governing critical seed traits. 相似文献
73.
P. N. Watton A. Selimovic N. B. Raberger P. Huang G. A. Holzapfel Y. Ventikos 《Biomechanics and modeling in mechanobiology》2011,10(1):109-132
A fluid–solid-growth (FSG) model of saccular cerebral aneurysm evolution is developed. It utilises a realistic two-layered
structural model of the internal carotid artery and explicitly accounts for the degradation of the elastinous constituents
and growth and remodelling (G&R) of the collagen fabric. Aneurysm inception is prescribed: a localised degradation of elastin
results in a perturbation in the arterial geometry; the collagen fabric adapts, and the artery achieves a new homeostatic
configuration. The perturbation to the geometry creates an altered haemodynamic environment. Subsequent degradation of elastin
is explicitly linked to low wall shear stress (WSS) in a confined region of the arterial domain. A sidewall saccular aneurysm
develops, the collagen fabric adapts and the aneurysm stabilises in size. A quasi-static analysis is performed to determine
the geometry at diastolic pressure. This enables the cyclic stretching of the tissue to be quantified, and we propose a novel
index to quantify the degree of biaxial stretching of the tissue. Whilst growth is linked to low WSS from a steady (systolic)
flow analysis, a pulsatile flow analysis is performed to compare steady and pulsatile flow parameters during evolution. This
model illustrates the evolving mechanical environment for an idealised saccular cerebral aneurysm developing on a cylindrical
parent artery and provides the guidance to more sophisticated FSG models of aneurysm evolution which link G&R to the local
mechanical stimuli of vascular cells. 相似文献
74.
C. O'Brien L. Unruh C. Zimmerman W. E. Bradshaw C. M. Holzapfel W. A. Cresko 《Journal of fish biology》2013,82(3):827-839
Controlled laboratory experiments were used to show that Oregon and Alaskan three‐spined stickleback Gasterosteus aculeatus, collected from locations differing by 18° of latitude, exhibited no significant variation in length of the polyglutamine domain of the clock protein or in photoperiodic response within or between latitudes despite the fact that male and female G. aculeatus are photoperiodic at both latitudes. Hence, caution is urged when interpreting variation in the polyglutamine repeat (PolyQ) domain of the gene clock in the context of seasonal activities or in relationship to photoperiodism along geographical gradients. 相似文献
75.
Campbell CD Sampas N Tsalenko A Sudmant PH Kidd JM Malig M Vu TH Vives L Tsang P Bruhn L Eichler EE 《American journal of human genetics》2011,(3):1102-332
Copy-number variants (CNVs) can reach appreciable frequencies in the human population, and recent discoveries have shown that several of these copy-number polymorphisms (CNPs) are associated with human diseases, including lupus, psoriasis, Crohn disease, and obesity. Despite new advances, significant biases remain in terms of CNP discovery and genotyping. We developed a method based on single-channel intensity data and benchmarked against copy numbers determined from sequencing read depth to successfully obtain CNP genotypes for 1495 CNPs from 487 human DNA samples of diverse ethnic backgrounds. This microarray contained CNPs in segmental duplication-rich regions and insertions of sequences not represented in the reference genome assembly or on standard SNP microarray platforms. We observe that CNPs in segmental duplications are more likely to be population differentiated than CNPs in unique regions (p = 0.015) and that biallelic CNPs show greater stratification when compared to frequency-matched SNPs (p = 0.0026). Although biallelic CNPs show a strong correlation of copy number with flanking SNP genotypes, the majority of multicopy CNPs do not (40% with r > 0.8). We selected a subset of CNPs for further characterization in 1876 additional samples from 62 populations; this revealed striking population-differentiated structural variants in genes of clinical significance such as OCLN, a tight junction protein involved in hepatitis C viral entry. Our microarray design allows these variants to be rapidly tested for disease association and our results suggest that CNPs (especially those that cannot be imputed from SNP genotypes) might have contributed disproportionately to human diversity and selection. 相似文献
76.
Amelia Maika Murthy N. Mittinty Sally Brinkman Sam Harper Elan Satriawan John W. Lynch 《PloS one》2013,8(10)
Background
Measuring social inequalities in health is common; however, research examining inequalities in child cognitive function is more limited. We investigated household expenditure-related inequality in children’s cognitive function in Indonesia in 2000 and 2007, the contributors to inequality in both time periods, and changes in the contributors to cognitive function inequalities between the periods.Methods
Data from the 2000 and 2007 round of the Indonesian Family Life Survey (IFLS) were used. Study participants were children aged 7–14 years (n = 6179 and n = 6680 in 2000 and 2007, respectively). The relative concentration index (RCI) was used to measure the magnitude of inequality. Contribution of various contributors to inequality was estimated by decomposing the concentration index in 2000 and 2007. Oaxaca-type decomposition was used to estimate changes in contributors to inequality between 2000 and 2007.Results
Expenditure inequality decreased by 45% from an RCI = 0.29 (95% CI 0.22 to 0.36) in 2000 to 0.16 (95% CI 0.13 to 0.20) in 2007 but the burden of poorer cognitive function was higher among the disadvantaged in both years. The largest contributors to inequality in child cognitive function were inequalities in per capita expenditure, use of improved sanitation and maternal high school attendance. Changes in maternal high school participation (27%), use of improved sanitation (25%) and per capita expenditures (18%) were largely responsible for the decreasing inequality in children’s cognitive function between 2000 and 2007.Conclusions
Government policy to increase basic education coverage for women along with economic growth may have influenced gains in children’s cognitive function and reductions in inequalities in Indonesia. 相似文献77.
78.
F. A. Oguntoyinbo A. I. Sanni C. M. A. P. Franz W. H. Holzapfel 《World journal of microbiology & biotechnology》2007,23(3):401-410
The Bacillus subtilis wild strains isolated from okpehe, a traditional fermented condiment used as seasoning in Nigeria, the reference and typed strains were investigated for their
phenotypic diversity and their technological parameters with a view to obtain adequate data that would enable selection of
appropriated starter cultures for vegetable protein fermentation in West Africa. All the 7 strains studied demonstrated diverse
phenotypic characteristics and they were identified as Bacillus subtilis, based on the API 50 CHB combined with API 20E profile. Specific sugars that indicated a good hydrolytic potential of the
wild strains were fermented. The highest proteinase activity of 90 AU/ml determined quantitatively was observed in the strain
Bacillus subtilis BFE 5372, the proteinase was identified by the APIZYM gallery as chymotrypsin. Highest amylase activity of 13 AU/ml was noticed
in strain Bacillus subtilis DSM 347 while only 4 strains produced polyglutamic acid with the strain Bacillus subtilis BFE 5359 producing the highest polyglutamate activity of 2.5 mm. Although strain Bacillus subtilis BFE 5301 did not release detectable polyglutamate, the strain demonstrated antagonism against different bacteria and the
antimicrobial substance produced by strain Bacillus subtilis BFE 5301 was confirmed as a bacteriocin since its activities were lost after treatment with chymotrypsin and pepsin. The
data generated showed the technological parameters that can aid selection of wild strains such as Bacillus subtilis BFE 5301, BFE 5359 and BFE 5372 for optimization of condiment production. 相似文献
79.
Stress-strain analyses of vessel walls require appropriate constitutive equations. Determination of constitutive equations is based on experimental data of (i) diameter and length of a vessel segment subject to internal pressure and external axial force, and (ii) the load-free reference geometry. Typical clinical data, however, provide only pressure-diameter relations in the diastolic-systolic pressure range. In order to overcome this problem, an approach is proposed allowing the determination of constitutive equations from clinical data by means of reasonable assumptions regarding in situ configurations and stress states of arterial walls. The approach is based on a two-dimensional Fung-type stored-energy function capturing the characteristic nonlinear and anisotropic responses of arteries. Examples concerning human aortas from a normotensive and a hypertensive subject illustrate the potential of the approach. 相似文献
80.
Dennis MY Nuttle X Sudmant PH Antonacci F Graves TA Nefedov M Rosenfeld JA Sajjadian S Malig M Kotkiewicz H Curry CJ Shafer S Shaffer LG de Jong PJ Wilson RK Eichler EE 《Cell》2012,149(4):912-922
Gene duplication is an important source of phenotypic change and adaptive evolution. We leverage a haploid hydatidiform mole to identify highly identical sequences missing from the reference genome, confirming that the cortical development gene Slit-Robo Rho GTPase-activating protein 2 (SRGAP2) duplicated three times exclusively in humans. We show that the promoter and first nine exons of SRGAP2 duplicated from 1q32.1 (SRGAP2A) to 1q21.1 (SRGAP2B) ~3.4 million years ago (mya). Two larger duplications later copied SRGAP2B to chromosome 1p12 (SRGAP2C) and to proximal 1q21.1 (SRGAP2D) ~2.4 and ~1 mya, respectively. Sequence and expression analyses show that SRGAP2C is the most likely duplicate to encode a functional protein and is among the most fixed human-specific duplicate genes. Our data suggest a mechanism where incomplete duplication created a novel gene function-antagonizing parental SRGAP2 function-immediately "at birth" 2-3 mya, which is a time corresponding to the transition from Australopithecus to Homo and the beginning of neocortex expansion. 相似文献