全文获取类型
收费全文 | 348篇 |
免费 | 17篇 |
专业分类
365篇 |
出版年
2022年 | 6篇 |
2021年 | 3篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 7篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 23篇 |
2014年 | 14篇 |
2013年 | 21篇 |
2012年 | 32篇 |
2011年 | 33篇 |
2010年 | 26篇 |
2009年 | 14篇 |
2008年 | 32篇 |
2007年 | 31篇 |
2006年 | 27篇 |
2005年 | 16篇 |
2004年 | 15篇 |
2003年 | 5篇 |
2002年 | 16篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1989年 | 2篇 |
1981年 | 1篇 |
排序方式: 共有365条查询结果,搜索用时 0 毫秒
131.
In order to identify biomotor structures in elite female handball players, factor structures of morphological characteristics and basic motor abilities of elite female handball players (N = 53) were determined first, followed by determination of relations between the morphological-motor space factors obtained and the set of criterion variables evaluating situation motor abilities in handball. Factor analysis of 14 morphological measures produced three morphological factors, i.e. factor of absolute voluminosity (mesoendomorph), factor of longitudinal skeleton dimensionality, and factor of transverse hand dimensionality. Factor analysis of 15 motor variables yielded five basic motor dimensions, i.e. factor of agility, factor of jumping explosive strength, factor of throwing explosive strength, factor of movement frequency rate, and factor of running explosive strength (sprint). Four significant canonic correlations, i.e. linear combinations, explained the correlation between the set of eight latent variables of the morphological and basic motor space and five variables of situation motoricity. First canonic linear combination is based on the positive effect of the factors of agility/coordination on the ability of fast movement without ball. Second linear combination is based on the effect of jumping explosive strength and transverse hand dimensionality on ball manipulation, throw precision, and speed of movement with ball. Third linear combination is based on the running explosive strength determination by the speed of movement with ball, whereas fourth combination is determined by throwing and jumping explosive strength, and agility on ball pass. The results obtained were consistent with the model of selection in female handball proposed (Srhoj et al., 2006), showing the speed of movement without ball and the ability of ball manipulation to be the predominant specific abilities, as indicated by the first and second linear combination. 相似文献
132.
A cytosolic splice variant of Cab45 interacts with Munc18b and impacts on amylase secretion by pancreatic acini 总被引:2,自引:0,他引:2 下载免费PDF全文
Lam PP Hyvärinen K Kauppi M Cosen-Binker L Laitinen S Keränen S Gaisano HY Olkkonen VM 《Molecular biology of the cell》2007,18(7):2473-2480
We identified in a yeast two-hybrid screen the EF-hand Ca(2+)-binding protein Cab45 as an interaction partner of Munc18b. Although the full-length Cab45 resides in Golgi lumen, we characterize a cytosolic splice variant, Cab45b, expressed in pancreatic acini. Cab45b is shown to bind (45)Ca(2+), and, of its three EF-hand motifs, EF-hand 2 is demonstrated to be crucial for the ion binding. Cab45b is shown to interact with Munc18b in an in vitro assay, and this interaction is enhanced in the presence of Ca(2+). In this assay, Cab45b also binds the Munc18a isoform in a Ca(2+)-dependent manner. The endogenous Cab45b in rat acini coimmunoprecipitates with Munc18b, syntaxin 2, and syntaxin 3, soluble N-ethylmaleimide-sensitive factor attachment protein receptors with key roles in the Ca(2+)-triggered zymogen secretion. Furthermore, we show that Munc18b bound to syntaxin 3 recruits Cab45b onto the plasma membrane. Importantly, antibodies against Cab45b are shown to inhibit in a specific and dose-dependent manner the Ca(2+)-induced amylase release from streptolysin-O-permeabilized acini. The present study identifies Cab45b as a novel protein factor involved in the exocytosis of zymogens by pancreatic acini. 相似文献
133.
Sabrina Ait Braham Fouzia Hussain Roberto Morellon-Sterling Shagufta Kamal Jakub F. Kornecki Oveimar Barbosa Djamel Edine Kati Roberto Fernandez-Lafuente 《Biotechnology progress》2019,35(2):e2768
Alcalase was scarcely immobilized on monoaminoethyl-N-aminoethyl (MANAE)-agarose beads at different pH values (<20% at pH 7). The enzyme did not immobilize on MANAE-agarose activated with glutaraldehyde at high ionic strength, suggesting a low reactivity of the enzyme with the support functionalized in this manner. However, the immobilization is relatively rapid when using low ionic strength and glutaraldehyde activated support. Using these conditions, the enzyme was immobilized at pH 5, 7, and 9, and in all cases, the activity vs. Boc-Ala-ONp decreased to around 50%. However, the activity vs. casein greatly depends on the immobilization pH, while at pH 5 it is also 50%, at pH 7 it is around 200%, and at pH 9 it is around 140%. All immobilized enzymes were significantly stabilized compared to the free enzyme when inactivated at pH 5, 7, or 9. The highest stability was always observed when the enzyme was immobilized at pH 9, and the worst stability occurred when the enzyme was immobilized at pH 5, in agreement with the reactivity of the amino groups of the enzyme. Stabilization was lower for the three preparations when the inactivation was performed at pH 5. Thus, this is a practical example on how the cooperative effect of ion exchange and covalent immobilization may be used to immobilize an enzyme when only one independent cause of immobilization is unable to immobilize the enzyme, while adjusting the immobilization pH leads to very different properties of the final immobilized enzyme preparation. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2768, 2019. 相似文献
134.
Konstantina Zografou Vassiliki Kati Andrea Grill Robert J. Wilson Elli Tzirkalli Lazaros N. Pamperis John M. Halley 《PloS one》2014,9(1)
The European protected-area network will cease to be efficient for biodiversity conservation, particularly in the Mediterranean region, if species are driven out of protected areas by climate warming. Yet, no empirical evidence of how climate change influences ecological communities in Mediterranean nature reserves really exists. Here, we examine long-term (1998–2011/2012) and short-term (2011–2012) changes in the butterfly fauna of Dadia National Park (Greece) by revisiting 21 and 18 transects in 2011 and 2012 respectively, that were initially surveyed in 1998. We evaluate the temperature trend for the study area for a 22-year-period (1990–2012) in which all three butterfly surveys are included. We also assess changes in community composition and species richness in butterfly communities using information on (a) species’ elevational distributions in Greece and (b) Community Temperature Index (calculated from the average temperature of species'' geographical ranges in Europe, weighted by species'' abundance per transect and year). Despite the protected status of Dadia NP and the subsequent stability of land use regimes, we found a marked change in butterfly community composition over a 13 year period, concomitant with an increase of annual average temperature of 0.95°C. Our analysis gave no evidence of significant year-to-year (2011–2012) variability in butterfly community composition, suggesting that the community composition change we recorded is likely the consequence of long-term environmental change, such as climate warming. We observe an increased abundance of low-elevation species whereas species mainly occurring at higher elevations in the region declined. The Community Temperature Index was found to increase in all habitats except agricultural areas. If equivalent changes occur in other protected areas and taxonomic groups across Mediterranean Europe, new conservation options and approaches for increasing species’ resilience may have to be devised. 相似文献
135.
Marieta I. Toma Kati Erdmann Michael Diezel Matthias Meinhardt Stefan Zastrow Susanne Fuessel Manfred P. Wirth Gustavo B. Baretton 《PloS one》2014,9(7)
The EPH receptor tyrosine kinases and their cell-bound ligands, the ephrins, have been shown to be associated with cancer development and progression. In this study, mRNA and protein expression of the receptors EPHA1 and EPHA2 as well as of their ligand EFNA1 and their prognostic relevance in clear cell renal cell carcinoma was evaluated. Gene expression was measured in 75 cryo-preserved primary tumors and matched non-malignant renal specimens by quantitative PCR. Protein expression was analyzed by immunohistochemistry on tissue microarrays comprising non-malignant, primary tumors and metastatic renal tissues of 241 patients. Gene and protein expression of all three factors was altered in tumor specimens with EPHA1 and EPHA2 being generally diminished in tumors compared to normal renal tissue, whereas EFNA1 was commonly elevated. A positive EPHA1 and EPHA2 protein staining as well as a low EFNA1 protein level were significantly linked to more aggressive tumor features, but only a positive EPHA1 immunoreactivity was significantly associated with poor survival. In subgroup analyses, EPHA1 and EPHA2 protein levels were significantly higher in metastatic than in primary lesions. Patients with EPHA1/EPHA2-positive tumors or with tumors with positive EPHA1 and low EFNA1 immunoreactivity had the shortest survival rates compared to the respective other combinations. In a multivariate model, EPHA1 was an independent prognostic marker for different survival endpoints. In conclusion, an impaired EPH-ephrin signaling could contribute to the pathogenesis and progression of clear cell renal cell carcinoma. 相似文献
136.
Jari Lahti Marius Lahti Anu-Katriina Pesonen Kati Heinonen Eero Kajantie Tom Forsén Kristian Wahlbeck Clive Osmond David J. P. Barker Johan G. Eriksson Katri R?ikk?nen 《PloS one》2014,9(1)
Background
Small birth size - an indicator of a sub-optimal prenatal environment - and variation in growth after birth have been associated with non-communicable diseases in later life. We tested whether birth size or growth in childhood associated with the risk of hospital admission for alcohol use disorders (AUDs) from early to late adulthood.Methods
The sample comprised 6544 men and 6050 women born between 1934 and 1944 in Helsinki, Finland. Data on anthropometric measures were extracted from medical records and diagnoses of AUD from the Finnish Hospital Discharge Register and Causes of Death Register covering a 40-year period from 1969 to 2008.Results
Altogether 171 women (2.8%) and 657 men (10.0%) were diagnosed at a hospital with AUD. After adjusting for major confounders, shorter length at birth, shorter height up to two years of age, and lower weight at two years associated with hospitalization for AUD in women. In men, slower growth in height, particularly from 2 to 7 years, and slower weight gain from 7 to 11 years as well as shorter height and lower weight at 7 and 11 years associated with a diagnosis of AUD in men.Conclusions
Pre- and postnatal growth associates with the risk for AUD later in life differently in women than in men: the fetal period and infancy seem to be the sensitive periods for women, whereas those for men the occur from toddlerhood onwards. 相似文献137.
Lena Poppinga Bettina Janesch Anne Fünfhaus Gerhard Sekot Eva Garcia-Gonzalez Gillian Hertlein Kati Hedtke Christina Sch?ffer Elke Genersch 《PLoS pathogens》2012,8(5)
The Gram-positive, spore-forming bacterium Paenibacillus larvae is the etiological agent of American Foulbrood (AFB), a globally occurring, deathly epizootic of honey bee brood. AFB outbreaks are predominantly caused by two genotypes of P. larvae, ERIC I and ERIC II, with P. larvae ERIC II being the more virulent genotype on larval level. Recently, comparative proteome analyses have revealed that P. larvae ERIC II but not ERIC I might harbour a functional S-layer protein, named SplA. We here determine the genomic sequence of splA in both genotypes and demonstrate by in vitro self-assembly studies of recombinant and purified SplA protein in combination with electron-microscopy that SplA is a true S-layer protein self-assembling into a square 2D lattice. The existence of a functional S-layer protein is novel for this bacterial species. For elucidating the biological function of P. larvae SplA, a genetic system for disruption of gene expression in this important honey bee pathogen was developed. Subsequent analyses of in vivo biological functions of SplA were based on comparing a wild-type strain of P. larvae ERIC II with the newly constructed splA-knockout mutant of this strain. Differences in cell and colony morphology suggest that SplA is a shape-determining factor. Marked differences between P. larvae ERIC II wild-type and mutant cells with regard to (i) adhesion to primary pupal midgut cells and (ii) larval mortality as measured in exposure bioassays corroborate the assumption that the S-layer of P. larvae ERIC II is an important virulence factor. Since SplA is the first functionally proven virulence factor for this species, our data extend the knowledge of the molecular differences between these two genotypes of P. larvae and contribute to explaining the observed differences in virulence. These results present an immense advancement in our understanding of P. larvae pathogenesis. 相似文献
138.
Haploinsufficiency of SF3B4, a component of the pre-mRNA spliceosomal complex, causes Nager syndrome
Bernier FP Caluseriu O Ng S Schwartzentruber J Buckingham KJ Innes AM Jabs EW Innis JW Schuette JL Gorski JL Byers PH Andelfinger G Siu V Lauzon J Fernandez BA McMillin M Scott RH Racher H;FORGE Canada Consortium Majewski J Nickerson DA Shendure J Bamshad MJ Parboosingh JS 《American journal of human genetics》2012,90(5):925-933
Nager syndrome, first described more than 60 years ago, is the archetype of a class of disorders called the acrofacial dysostoses, which are characterized by craniofacial and limb malformations. Despite intensive efforts, no gene for Nager syndrome has yet been identified. In an international collaboration, FORGE Canada and the National Institutes of Health Centers for Mendelian Genomics used exome sequencing as a discovery tool and found that mutations in SF3B4, a component of the U2 pre-mRNA spliceosomal complex, cause Nager syndrome. After Sanger sequencing of SF3B4 in a validation cohort, 20 of 35 (57%) families affected by Nager syndrome had 1 of 18 different mutations, nearly all of which were frameshifts. These results suggest that most cases of Nager syndrome are caused by haploinsufficiency of SF3B4. Our findings add Nager syndrome to a growing list of disorders caused by mutations in genes that encode major components of the spliceosome and also highlight the synergistic potential of international collaboration when exome sequencing is applied in the search for genes responsible for rare Mendelian phenotypes. 相似文献
139.
The site specificity, extent, and nature of modification of the tetrapeptide, Leu-Ser-Lys-Leu (1), incubated with d-glucose or d-fructose in methanol, or in phosphate buffer of pH 5.7, 7.4, and 8.0 were investigated. The generated mono- and di-glycated Amadori (1-deoxy-d-fructosyl derivatives) and Heyns rearrangement products (N-alkylated glucosamine/mannosamine derivatives) were isolated and characterized by NMR and mass spectrometry. The results identified the epsilon-amino group of the Lys residue as the preferential glycation site in tetrapeptide 1. Under all conditions investigated, glucose afforded higher yields of glycation products than fructose. In the reactions carried out in buffer, glycation at pH 7.4 and 8.0 was much faster than at pH 5.7. 相似文献
140.
The aim of the study was to assess the development of motor abilities in elementary school fifth- to eighth-graders (age 11-14 years) according to sex, age and physical activity. Study sample included 312 subjects divided according to age and sex into four groups: male subjects aged 11-12 (n = 93) and 13-14 years (n = 84); and female subjects aged 11-12 (n = 65) and 13-14 years (n = 70). Then, differences in basic motor abilities between children included (experimental group) and those not included (control group) in swimming training were analyzed. In male fifth- and sixth-graders, experimental group was superior to control group in the variables of trunk repetitive strength, sprint, flexibility and coordination, while in male seventh- and eighth-graders experimental group showed better performance than control group in agility, aerobic endurance and explosive throw and jump strength. In female fifth- and sixth-graders, experimental group proved superior to control group in the variables of explosive strength, coordination, trunk strength and aerobic endurance, whereas in female seventh- and eighth-graders experimental group had better performance in coordination, endurance, explosive strength, speed and flexibility. Discriminative analysis of motor variables between male and female subjects revealed male subjects to be superior in explosive strength, throw strength in particular, coordination and aerobic endurance, whereas female subjects showed better performance in the variables of flexibility and movement frequency, leg movement in particular. Study results showed the formation of appropriate motor system determining achievement of top results in swimming to be influenced by swimming training from age 11 to 14. In male children, motor system was found to integrate coordination/agility, aerobic endurance and explosive strength, whereas in female children it integrated coordination in terms of cortical movement regulation, aerobic endurance, explosive strength and psychomotor speed. 相似文献