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71.
Stacy Gelhaus Wendell Franca Golin-Bisello Sally Wenzel Robert W. Sobol Fernando Holguin Bruce A. Freeman 《The Journal of biological chemistry》2015,290(9):5868-5880
15-Hydroxyprostaglandin dehydrogenase (15PGDH) is the primary enzyme catalyzing the conversion of hydroxylated arachidonic acid species to their corresponding oxidized metabolites. The oxidation of hydroxylated fatty acids, such as the conversion of prostaglandin (PG) E2 to 15-ketoPGE2, by 15PGDH is viewed to inactivate signaling responses. In contrast, the typically electrophilic products can also induce anti-inflammatory and anti-proliferative responses. This study determined that hydroxylated docosahexaenoic acid metabolites (HDoHEs) are substrates for 15PGDH. Examination of 15PGDH substrate specificity was conducted in cell culture (A549 and primary human airway epithelia and alveolar macrophages) using chemical inhibition and shRNA knockdown of 15PGDH. Substrate specificity is broad and relies on the carbon position of the acyl chain hydroxyl group. 14-HDoHE was determined to be the optimal DHA substrate for 15PGDH, resulting in the formation of its electrophilic metabolite, 14-oxoDHA. Consistent with this, 14-HDoHE was detected in bronchoalveolar lavage cells of mild to moderate asthmatics, and the exogenous addition of 14-oxoDHA to primary alveolar macrophages inhibited LPS-induced proinflammatory cytokine mRNA expression. These data reveal that 15PGDH-derived DHA metabolites are biologically active and can contribute to the salutary signaling actions of Ω-3 fatty acids. 相似文献
72.
MORAIS PAULO AMORIM ANTÓNIO VIEIRA DA SILVA CLÁUDIA RIBEIRO TERESA COSTA SANTOS JORGE AFONSO COSTA HELOÍSA 《Journal of genetics》2015,94(3):509-512
Journal of Genetics - 相似文献
73.
Anna Bauereiss Oliver Welzel Jasmin Jung Simon Grosse‐Holz Natalia Lelental Piotr Lewczuk Eva M. Wenzel Johannes Kornhuber Teja W. Groemer 《Traffic (Copenhagen, Denmark)》2015,16(6):655-675
Amyloid‐β (Aβ)‐peptide, the major constituent of the plaques that develop during Alzheimer's disease, is generated via the cleavage of Aβ precursor protein (APP) by β‐site APP‐cleaving enzyme (BACE). Using live‐cell imaging of APP and BACE labeled with pH‐sensitive proteins, we could detect the release events of APP and BACE and their distinct kinetics. We provide kinetic evidence for the cleavage of APP by α‐secretase on the cellular surface after exocytosis. Furthermore, simultaneous dual‐color evanescent field illumination revealed that the two proteins are trafficked to the surface in separate compartments. Perturbing the membrane lipid composition resulted in a reduced frequency of exocytosis and affected BACE more strongly than APP. We propose that surface fusion frequency is a key factor regulating the aggregation of APP and BACE in the same membrane compartment and that this process can be modulated via pharmacological intervention. 相似文献
74.
Integration of BpMADS4 on various linkage groups improves the utilization of the rapid cycle breeding system in apple 总被引:1,自引:0,他引:1
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Kathleen Weigl Stephanie Wenzel Henryk Flachowsky Andreas Peil Magda‐Viola Hanke 《Plant biotechnology journal》2015,13(2):246-258
Rapid cycle breeding in apple is a new approach for the rapid introgression of agronomically relevant traits (e.g. disease resistances) from wild apple species into domestic apple cultivars (Malus × domestica Borkh.). This technique drastically shortens the long‐lasting juvenile phase of apple. The utilization of early‐flowering apple lines overexpressing the BpMADS4 gene of the European silver birch (Betula pendula Roth.) in hybridization resulted in one breeding cycle per year. Aiming for the selection of non‐transgenic null segregants at the end of the breeding process, the flower‐inducing transgene and the gene of interest (e.g. resistance gene) that will be introgressed by hybridization need to be located on different chromosomes. To improve the flexibility of the existing approach in apple, this study was focused on the development and characterization of eleven additional BpMADS4 overexpressing lines of four different apple cultivars. In nine lines, the flowering gene was mapped to different linkage groups. The differences in introgressed T‐DNA sequences and plant genome deletions post‐transformation highlighted the unique molecular character of each line. However, transgenic lines demonstrated no significant differences in flower organ development and pollen functionality compared with non‐transgenic plants. Hybridization studies using pollen from the fire blight‐resistant wild species accession Malus fusca MAL0045 and the apple scab‐resistant cultivar ‘Regia’ indicated that BpMADS4 introgression had no significant effect on the breeding value of each transgenic line. 相似文献
75.
76.
Comhair SA Gaston BM Ricci KS Hammel J Dweik RA Teague WG Meyers D Ampleford EJ Bleecker ER Busse WW Calhoun WJ Castro M Chung KF Curran-Everett D Israel E Jarjour WN Moore W Peters SP Wenzel S Hazen SL Erzurum SC;National Heart Lung Blood Institute Severe Asthma Research Program 《PloS one》2011,6(5):e18574
Background
Environmental tobacco smoke (ETS) has adverse effects on the health of asthmatics, however the harmful consequences of ETS in relation to asthma severity are unknown.Methods
In a multicenter study of severe asthma, we assessed the impact of ETS exposure on morbidity, health care utilization and lung functions; and activity of systemic superoxide dismutase (SOD), a potential oxidative target of ETS that is negatively associated with asthma severity.Findings
From 2002–2006, 654 asthmatics (non-severe 366, severe 288) were enrolled, among whom 109 non-severe and 67 severe asthmatics were routinely exposed to ETS as ascertained by history and validated by urine cotinine levels. ETS-exposure was associated with lower quality of life scores; greater rescue inhaler use; lower lung function; greater bronchodilator responsiveness; and greater risk for emergency room visits, hospitalization and intensive care unit admission. ETS-exposure was associated with lower levels of serum SOD activity, particularly in asthmatic women of African heritage.Interpretation
ETS-exposure of asthmatic individuals is associated with worse lung function, higher acuity of exacerbations, more health care utilization, and greater bronchial hyperreactivity. The association of diminished systemic SOD activity to ETS exposure provides for the first time a specific oxidant mechanism by which ETS may adversely affect patients with asthma. 相似文献77.
Song YS Hepting L Schweizer G Hartl L Wenzel G Schwarzfischer A 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,111(5):879-887
The inheritance of extreme resistance to PVY (Ry
sto) by a single dominant locus was confirmed by obtaining a 1:1 segregation ratio in a virus inoculation test with 28 resistant
(Ryry) to 29 susceptible (ryry) anther culture-derived dihaploid lines (2n=2x=24) from cv. “Assia” (2n=4x=48) having extreme resistance derived from Solanum stoloniferum in simplex constitution (Ryryryry). Twelve Ry
sto markers selected in AFLP assays using bulked segregant analysis were applied to 106 tested potato cultivars from Germany,
The Netherlands and Poland and 19 potato cultivars were identified by these markers as extremely resistant to PVY in alignment
with phenotypic data. The locus for extreme resistance (Ry
sto) to PVY was mapped on chromosome XII co-segregating with the SSR marker STM0003. The utility of anther-culture derived dihaploid
potatoes for genetic marker development was demonstrated. Marker transferability from diploids to tetraploids provides an
optimistic potential for marker-assisted selection in potato breeding programs. 相似文献
78.
We investigate the landscape of the internal free-energy of the 36 amino acid villin headpiece with a modified basin hopping method in the all-atom force field PFF01, which was previously used to predictively fold several helical proteins with atomic resolution. We identify near native conformations of the protein as the global optimum of the force field. More than half of the twenty best simulations started from random initial conditions converge to the folding funnel of the native conformation, but several competing low-energy metastable conformations were observed. From 76,000 independently generated conformations we derived a decoy tree which illustrates the topological structure of the entire low-energy part of the free-energy landscape and characterizes the ensemble of metastable conformations. These emerge as similar in secondary content, but differ in tertiary arrangement. 相似文献
79.
Formation of novel secondary metabolites by bacterial multimodular assembly lines: deviations from textbook biosynthetic logic 总被引:4,自引:0,他引:4
Microorganisms produce an immense variety of natural products with useful biological activities. These compounds are often biosynthesized by multifunctional megasynthetases known as polyketide synthases and nonribosomal peptide synthetases. Recent literature on these natural product assembly lines suggests that they have a much greater mechanistic diversity than originally anticipated. 相似文献
80.
Preusser-Kunze A Mariappan M Schmidt B Gande SL Mutenda K Wenzel D von Figura K Dierks T 《The Journal of biological chemistry》2005,280(15):14900-14910
Calpha-formylglycine (FGly) is the catalytic residue in the active site of sulfatases. In eukaryotes, it is generated in the endoplasmic reticulum by post-translational modification of a conserved cysteine residue. The FGly-generating enzyme (FGE), performing this modification, is an endoplasmic reticulum-resident enzyme that upon overexpression is secreted. Recombinant FGE was purified from cells and secretions to homogeneity. Intracellular FGE contains a high mannose type N-glycan, which is processed to the complex type in secreted FGE. Secreted FGE shows partial N-terminal trimming up to residue 73 without loosing catalytic activity. FGE is a calcium-binding protein containing an N-terminal (residues 86-168) and a C-terminal (residues 178-374) protease-resistant domain. The latter is stabilized by three disulfide bridges arranged in a clamp-like manner, which links the third to the eighth, the fourth to the seventh, and the fifth to the sixth cysteine residue. The innermost cysteine pair is partially reduced. The first two cysteine residues are located in the sequence preceding the N-terminal protease-resistant domain. They can form intramolecular or intermolecular disulfide bonds, the latter stabilizing homodimers. The C-terminal domain comprises the substrate binding site, as evidenced by yeast two-hybrid interaction assays and photocross-linking of a substrate peptide to proline 182. Peptides derived from all known human sulfatases served as substrates for purified FGE indicating that FGE is sufficient to modify all sulfatases of the same species. 相似文献