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201.
202.
Kaiser L Velickovic TC Badia-Martinez D Adedoyin J Thunberg S Hallén D Berndt K Grönlund H Gafvelin G van Hage M Achour A 《Journal of molecular biology》2007,370(4):714-727
Felis domesticus allergen 1(Fel d 1) is a 35 kDa tetrameric glycoprotein formed by two heterodimers which elicits IgE responses in 95% of patients with allergy to cat. We have previously established in vitro conditions for the appropriate folding of recombinant Fel d 1 using a direct linkage of chain 1 to chain 2 (construct Fel d 1 (1+2)) and chain 2 to chain 1 (construct Fel d 1 (2+1)). Although the crystal structure of Fel d 1 (2+1) revealed a striking structural similarity to that of uteroglobin, a steroid-inducible cytokine-like molecule with anti-inflammatory and immunomodulatory properties, no functional tetrameric form of Fel d 1 could be identified. Here we present the crystal structure of the Fel d 1 (1+2) tetramer at 1.6 A resolution. Interestingly, the crystal structure of tetrameric Fel d 1 reveals two different calcium-binding sites. Symmetrically positioned on each side of the Fel d 1 tetramer, the external Ca(2+)-binding sites correspond to a putative Ca(2+)-binding site previously suggested for uteroglobin. The second Ca(2+)-binding site lies within the dimerization interface, stabilizing the formation of the Fel d 1 tetramer, and inducing important local conformational changes that directly govern the shape of two water-filled cavities. The crystal structure suggests a potential portal for an unknown ligand. Alternatively, the two cavities could be used by the allergen as a conditional inner space allowing for the spatial rearrangement of centrally localized side-chains, such as Asp130, without altering the overall fold of the molecule. The striking structural similarity of the major cat allergen to uteroglobin, coupled to the identification in the present study of a common Ca(2+)-binding site, let us speculate that Fel d 1 could provoke an allergic response through the modulation of phospholipase A2, by sequestering Ca ions in a similar manner as previously suggested for uteroglobin. 相似文献
203.
Torben Haugaard Jensen Martin Bech Tina Binderup Arvid B?ttiger Christian David Timm Weitkamp Irene Zanette Elena Reznikova Jürgen Mohr Fritz Rank Robert Feidenhans’l Andreas Kj?r Liselotte H?jgaard Franz Pfeiffer 《PloS one》2013,8(1)
Invasive cancer causes a change in density in the affected tissue, which can be visualized by x-ray phase-contrast tomography. However, the diagnostic value of this method has so far not been investigated in detail. Therefore, the purpose of this study was, in a blinded manner, to investigate whether malignancy could be revealed by non-invasive x-ray phase-contrast tomography in lymph nodes from breast cancer patients. Seventeen formalin-fixed paraffin-embedded lymph nodes from 10 female patients (age range 37–83 years) diagnosed with invasive ductal carcinomas were analyzed by X-ray phase-contrast tomography. Ten lymph nodes had metastatic deposits and 7 were benign. The phase-contrast images were analyzed according to standards for conventional CT images looking for characteristics usually only visible by pathological examinations. Histopathology was used as reference. The result of this study was that the diagnostic sensitivity of the image analysis for detecting malignancy was 100% and the specificity was 87%. The positive predictive value was 91% for detecting malignancy and the negative predictive value was 100%. We conclude that x-ray phase-contrast imaging can accurately detect density variations to obtain information regarding lymph node involvement previously inaccessible with standard absorption x-ray imaging. 相似文献
204.
Wijngaard CC Asten Lv Koopmans MP Pelt Wv Nagelkerke NJ Wielders CC Lier Av Hoek Wv Meijer A Donker GA Dijkstra F Harmsen C Sande MA Kretzschmar M 《PloS one》2012,7(2):e31197
Background
We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed – and thus an underestimation – whereas seasonal influenza mortality is often more inclusively estimated. For a valid comparison, our study used the same statistical methodology and data types to estimate pandemic and seasonal influenza mortality.Methods and Findings
We used data on all-cause mortality (1999–2010, 100% coverage, 16.5 million Dutch population) and influenza-like-illness (ILI) incidence (0.8% coverage). Data was aggregated by week and age category. Using generalized estimating equation regression models, we attributed mortality to influenza by associating mortality with ILI-incidence, while adjusting for annual shifts in association. We also adjusted for respiratory syncytial virus, hot/cold weather, other seasonal factors and autocorrelation. For the 2009 pandemic season, we estimated 612 (range 266–958) influenza-attributed deaths; for seasonal influenza 1,956 (range 0–3,990). 15,845 years-of-life-lost were estimated for the pandemic; for an average seasonal epidemic 17,908. For 0–4 yrs of age the number of influenza-attributed deaths during the pandemic were higher than in any seasonal epidemic; 77 deaths (range 61–93) compared to 16 deaths (range 0–45). The ≥75 yrs of age showed a far below average number of deaths. Using pneumonia/influenza and respiratory/cardiovascular instead of all-cause deaths consistently resulted in relatively low total pandemic mortality, combined with high impact in the youngest age category.Conclusion
The pandemic had an overall moderate impact on mortality compared to 10 preceding seasonal epidemics, with higher mortality in young children and low mortality in the elderly. This resulted in a total number of pandemic deaths far below the average for seasonal influenza, and a total number of years-of-life-lost somewhat below average. Comparing pandemic and seasonal influenza mortality as in our study will help assessing the worldwide impact of the 2009 pandemic. 相似文献205.
Jensen LE Wall AM Cook M Hoess K Thorn CF Whitehead AS Mitchell LE 《Birth defects research. Part A, Clinical and molecular teratology》2004,70(6):396-399
BACKGROUND: There is compelling evidence that the risk of spina bifida, a malformation of the caudal neural tube, is associated with maternal and/or embryonic disturbances in folate/homocysteine metabolism. Hence, functional variants of genes that influence folate/homocysteine metabolism constitute a biologically plausible group of candidate risk factors for spina bifida and other neural tube defects. One such candidate is ABCC2, the gene encoding ABCC2, (a.k.a. canalicular multispecific organic anion transporter [cMOAT], multidrug resistance related protein 2 [MRP2]), a member of the ABC transporter family that effluxes natural folates and anti-folate drugs such as methotrexate. METHODS: The association between the risk of spina bifida and both the maternal and embryonic ABCC2 C(-24)T genotype was evaluated by using the transmission disequilibrium test and log-linear modeling. RESULTS: These analyses provided no evidence that the risk of spina bifida was significantly related to either the maternal or embryonic ABCC2 C(-24)T genotype. CONCLUSIONS: The results of the present analyses suggest that the C(-24)T variant of the ABCC2 gene is not a major determinant of spina bifida risk. 相似文献
206.
PUROMYCIN RESISTANCE IN HAPLOID AND HETEROPLOID FROG CELLS: GENE OR MEMBRANE DETERMINED? 总被引:4,自引:0,他引:4
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Liselotte Mezger-Freed 《The Journal of cell biology》1971,51(3):742-751
The frequency of colony formation in monolayers of cultured frog cell lines treated with puromycin was compared in (a) haploid and heteroploid lines and (b) mutagen-treated and nontreated haploid lines. Evidence that resistant colonies result from gene mutation was negative, since the colony frequency is independent of both ploidy and mutagen treatment. A study of five frog cell lines showed that colony formation in puromycin depends on (a) the concentration of puromycin, (b) preselection of the population with puromycin, and, particularly, (c) the capacity of the treated population to survive some exposure to puromycin. One haploid and one heteroploid strain showing stable resistance to puromycin have been isolated; comparison of those variants with sensitive populations has shown that resistance to puromycin is correlated with the cells' capacity to exclude the drug. The evidence for different levels of membrane permeability, combined with evidence for many degrees of resistance among and within cell populations, suggests a model of self-determining membrane units. The evolution of a resistant phenotype may result from changes in the proportion of specific units in the membrane population. 相似文献
207.
Martina Ozan Heikki Helanter? Liselotte Sundstr?m 《Proceedings. Biological sciences / The Royal Society》2013,280(1766)
Reproductive cooperation confers benefits, but simultaneously creates conflicts among cooperators. Queens in multi-queen colonies of ants share a nest and its resources, but reproductive competition among queens often results in unequal reproduction. Two mutually non-exclusive factors may produce such inequality in reproduction: worker intervention or queen traits. Workers may intervene by favouring some queens over others, owing to either kinship or queen signals. Queens may differ in their intrinsic fecundity at the onset of oviposition or in their timing of the onset of oviposition, leading to their unequal representation in the brood. Here, we test the role of queen kin value (relatedness) to workers, timing of the onset of oviposition and signals of presence by queens in determining the maternity of offspring. We show that queens of the ant Formica fusca gained a significantly higher proportion of sexuals in the brood when ovipositing early, and that the presence of a caged queen resulted in a significant increase in both her share of sexual brood and her overall reproductive share. Moreover, the lower the kin value of the queen, the more the workers invested in their own reproduction by producing males. Our results show that both kinship and breeding phenology influence the outcome of reproductive conflicts, and the balance of direct and indirect fitness benefits in the multi-queen colonies of F. fusca. 相似文献
208.
Georg Wolfram Christine Argillier Julien de Bortoli Fabio Buzzi Antonio Dalmiglio Martin T. Dokulil Eberhard Hoehn Aldo Marchetto Pierre-Jean Martinez Giuseppe Morabito Markus Reichmann Špela Remec-Rekar Ursula Riedmüller Christelle Rioury Jochen Schaumburg Liselotte Schulz Gorazd Urbanič 《Hydrobiologia》2009,633(1):45-58
The intercalibration (IC) exercise is a key element in the implementation of the Water Framework Directive (WFD) in Europe. Its focus lies on the harmonization of national classification methods to guarantee a common understanding of ‘Good Ecological Status’ in surface waters. This article defines reference conditions and sets class boundaries for deep (mean depth >15 m, IC lake type L-AL3) and moderately deep (mean depth 3–15 m, IC lake type L-AL4) Alpine lakes >0.5 km2. Data were collated from each of the five EU member states included in the Alpine Geographical Intercalibration Group (Alpine GIG: Austria, France, Germany, Italy and Slovenia). Hydro-morphological, chemical and biological data from 161 sites (sampling stations) in 144 Alpine lakes over a period of seven decades were collated in a database. Based on a set of reference criteria, 18 L-AL3 and 13 L-AL4 reference sites were selected. Reference conditions were defined using a combined approach, based on historical, paleolimnological and monitoring data in conjunction with trophic modelling and expert judgement. Reference values and class boundaries were set for annual mean total biomass (biovolume), and then derived for annual mean chlorophyll-a using a regression between the two parameters. In order to allow for geographical differences within the Alpine GIG and to facilitate the inclusion of the broadly defined common IC types and national lake types, ranges were defined for each reference value. Range of reference values are 0.2–0.3 mg l?1 (L-AL3) and 0.5–0.7 mg l?1 (L-AL4) for total biovolume and 1.5–1.9 μg l?1 (L-AL3) and 2.7–3.3 μg l?1 (L-AL4) for chlorophyll-a. Depending on lake type and variable, the ecological quality ratios (EQR) for setting the class boundaries lie between 0.60 and 0.75 for the high/good class boundary and between 0.25 and 0.41 for the good/moderate class boundary. The response of sensitive phytoplankton taxa along a nutrient gradient and the occurrence of ‘undesirable conditions and secondary effects’ as defined in the WFD was used to validate the class boundary values, which are thus considered to be compliant with the requirements of the WFD. 相似文献
209.
Glycosides of glucose and lactose with di- and tetraethylene glycols, transformed into bifunctional (alcohol, ester) spacer molecules, have been synthesized. After deprotection, these spacer glycosides, containing a free carboxyl group, have been transformed efficiently into glycoconjugates usingN,N,N,N-tetramethyl(succinimido)uronium tetrafluoroborate (TSTU) for the formation of an active ester. 相似文献
210.
Britt-Marie Swahn Istvan Macsari Jenny Viklund Liselotte Öhberg Johanna Sjödin Jan Neelissen Johanna Lindquist 《Bioorganic & medicinal chemistry letters》2009,19(7):2009-2012
The synthesis and SAR of a new series of LXR agonist is reported. The N-Aryl-3,3,3-trifluoro-2-hydroxy-2-methyl-propionamide hits were found in a limited screen of the AstraZeneca compound collection. The effort to optimize these hits into LXRβ selectivity is described. Compound 20 displayed desirable pharmacokinetic profile and up regulation of ABCA1 and ABCG1 mRNA in the brain were achieved when evaluated in vivo in mice. 相似文献