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31.
Marie Abitbol Christophe Hitte Philippe Bossé Nicolas Blanchard-Gutton Anne Thomas Lionel Martignat Stéphane Blot Laurent Tiret 《PloS one》2015,10(9)
An autosomal recessive neuromuscular disorder characterized by skeletal muscle weakness, fatigability and variable electromyographic or muscular histopathological features has been described in the two related Sphynx and Devon Rex cat breeds (Felis catus). Collection of data from two affected Sphynx cats and their relatives pointed out a single disease candidate region on feline chromosome C2, identified following a genome-wide SNP-based homozygosity mapping strategy. In that region, we further identified COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase) as a good candidate gene, since COLQ mutations were identified in affected humans and dogs with endplate acetylcholinesterase deficiency leading to a synaptic form of congenital myasthenic syndrome (CMS). A homozygous c.1190G>A missense variant located in exon 15 of COLQ, leading to a C397Y substitution, was identified in the two affected cats. C397 is a highly-conserved residue from the C-terminal domain of the protein; its mutation was previously shown to produce CMS in humans, and here we confirmed in an affected Sphynx cat that it induces a loss of acetylcholinesterase clustering at the neuromuscular junction. Segregation of the c.1190G>A variant was 100% consistent with the autosomal recessive mode of inheritance of the disorder in our cat pedigree; in addition, an affected, unrelated Devon Rex cat recruited thereafter was also homozygous for the variant. Genotyping of a panel of 333 cats from 14 breeds failed to identify a single carrier in non-Sphynx and non-Devon Rex cats. Finally, the percentage of healthy carriers in a European subpanel of 81 genotyped Sphynx cats was estimated to be low (3.7%) and 14 control Devon Rex cats were genotyped as wild-type individuals. Altogether, these results strongly support that the neuromuscular disorder reported in Sphynx and Devon Rex breeds is a CMS caused by a unique c.1190G>A missense mutation, presumably transmitted through a founder effect, which strictly and slightly disseminated in these two breeds. The presently available DNA test will help owners avoid matings at risk. 相似文献
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33.
Biological control as an alternative to chemical pesticides is of increasing public interest. However, to ensure safe use of biocontrol methods, strategies to assess the possible risks need to be developed. The production of toxic metabolites is an aspect which has so far largely been neglected in the risk assessment and the registration process for biocontrol products. We have evaluated the risks of elsinochrome A (ELA) and leptosphaerodione production by the fungus Stagonospora convolvuli LA39, an effective biocontrol agent used against bindweeds. The toxicity of the two metabolites to bacteria, protozoa, fungi and plants was evaluated in in vitro assays. The most sensitive bacteria and fungi were already affected at 0.01-0.07 microM ELA, whereas plants were far less sensitive. Leptosphaerodione was less toxic than ELA. Subsequently, it was investigated whether ELA is present in the applied biocontrol product or LA39-treated bindweed and crop plants. In plants ELA was never detected and in the biocontrol product the ELA concentration was far too low to have toxic effects even on the most sensitive organisms. We conclude that the production of ELA by biocontrol strain LA39 does not pose a risk to the environment or to the consumer. 相似文献
34.
35.
Davis AJ Im YJ Dubin JS Tomer KB Boss WF 《The Journal of biological chemistry》2007,282(19):14121-14131
The actin cytoskeleton can be influenced by phospholipids and lipid-modifying enzymes. In animals the phosphatidylinositol phosphate kinases (PIPKs) are associated with the cytoskeleton through a scaffold of proteins; however, in plants such an interaction was not clear. Our approach was to determine which of the plant PIPKs interact with actin and determine whether the PIPK-actin interaction is direct. Our results indicate that AtPIPK1 interacts directly with actin and that the binding is mediated through a predicted linker region in the lipid kinase. AtPIPK1 also recruits AtPI4Kbeta1 to the cytoskeleton. Recruitment of AtPI4Kbeta1 to F-actin was dependent on the C-terminal catalytic domain of phosphatidylinositol-4-phosphate 5-kinase but did not require the presence of the N-terminal 251 amino acids, which includes 7 putative membrane occupation and recognition nexus motifs. In vivo studies confirm the interaction of plant lipid kinases with the cytoskeleton and suggest a role for actin in targeting PIPKs to the membrane. 相似文献
36.
Seasonal nutrient and plankton dynamics in a physical-biological model of Crater Lake 总被引:1,自引:1,他引:0
Katja Fennel Robert Collier Gary Larson Greg Crawford Emmanuel Boss 《Hydrobiologia》2007,574(1):265-280
A coupled 1D physical-biological model of Crater Lake is presented. The model simulates the seasonal evolution of two functional
phytoplankton groups, total chlorophyll, and zooplankton in good quantitative agreement with observations from a 10-year monitoring
study. During the stratified period in summer and early fall the model displays a marked vertical structure: the phytoplankton
biomass of the functional group 1, which represents diatoms and dinoflagellates, has its highest concentration in the upper
40 m; the phytoplankton biomass of group 2, which represents chlorophyta, chrysophyta, cryptomonads and cyanobacteria, has
its highest concentrations between 50 and 80 m, and phytoplankton chlorophyll has its maximum at 120 m depth. A similar vertical
structure is a reoccurring feature in the available data. In the model the key process allowing a vertical separation between
biomass and chlorophyll is photoacclimation. Vertical light attenuation (i.e., water clarity) and the physiological ability
of phytoplankton to increase their cellular chlorophyll-to-biomass ratio are ultimately determining the location of the chlorophyll
maximum. The location of the particle maxima on the other hand is determined by the balance between growth and losses and
occurs where growth and losses equal. The vertical particle flux simulated by our model agrees well with flux measurements
from a sediment trap. This motivated us to revisit a previously published study by Dymond et al. (1996). Dymond et al. used a box model to estimate the vertical particle flux and found a discrepancy by a factor 2.5–10 between
their model-derived flux and measured fluxes from a sediment trap. Their box model neglected the exchange flux of dissolved
and suspended organic matter, which, as our model and available data suggests is significant for the vertical exchange of
nitrogen. Adjustment of Dymond et al.’s assumptions to account for dissolved and suspended nitrogen yields a flux estimate
that is consistent with sediment trap measurements and our model. 相似文献
37.
David Gendron Anne-Marie Lemay Claudine Tremblay Laetitia JA Lai Anick Langlois émilie Bernatchez Nicolas Flamand Marie-Renée Blanchet Anthony S Don Ynuk Bossé élyse Bissonnette David Marsolais 《Respiratory research》2015,16(1)
Background
In vivo phosphorylation of sphingosine analogs with their ensuing binding and activation of their cell-surface sphingosine-1-phosphate receptors is regarded as the main immunomodulatory mechanism of this new class of drugs. Prophylactic treatment with sphingosine analogs interferes with experimental asthma by impeding the migration of dendritic cells to draining lymph nodes. However, whether these drugs can also alleviate allergic airway inflammation after its onset remains to be determined. Herein, we investigated to which extent and by which mechanisms the sphingosine analog AAL-R interferes with key features of asthma in a murine model during ongoing allergic inflammation induced by Dermatophagoides pteronyssinus.Methods
BALB/c mice were exposed to either D. pteronyssinus or saline, intranasally, once-daily for 10 consecutive days. Mice were treated intratracheally with either AAL-R, its pre-phosphorylated form AFD-R, or the vehicle before every allergen challenge over the last four days, i.e. after the onset of allergic airway inflammation. On day 11, airway responsiveness to methacholine was measured; inflammatory cells and cytokines were quantified in the airways; and the numbers and/or viability of T cells, B cells and dendritic cells were assessed in the lungs and draining lymph nodes.Results
AAL-R decreased airway hyperresponsiveness induced by D. pteronyssinus by nearly 70%. This was associated with a strong reduction of IL-5 and IL-13 levels in the airways and with a decreased eosinophilic response. Notably, the lung CD4+ T cells were almost entirely eliminated by AAL-R, which concurred with enhanced apoptosis/necrosis in that cell population. This inhibition occurred in the absence of dendritic cell number modulation in draining lymph nodes. On the other hand, the pre-phosphorylated form AFD-R, which preferentially acts on cell-surface sphingosine-1-phosphate receptors, was relatively impotent at enhancing cell death, which led to a less efficient control of T cell and eosinophil responses in the lungs.Conclusion
Airway delivery of the non-phosphorylated sphingosine analog, but not its pre-phosphorylated counterpart, is highly efficient at controlling the local T cell response after the onset of allergic airway inflammation. The mechanism appears to involve local induction of lymphocyte apoptosis/necrosis, while mildly affecting dendritic cell and T cell accumulation in draining lymph nodes. 相似文献38.
Background
A recent epidemiological study demonstrated a reduced risk of lung cancer mortality in breast cancer patients using antiestrogens. These and other data implicate a role for estrogens in lung cancer, particularly nonsmall cell lung cancer (NSCLC). Approximately 61% of human NSCLC tumors express nuclear estrogen receptor β (ERβ); however, the role of ERβ and estrogens in NSCLC is likely to be multifactorial. Here we tested the hypothesis that proteins interacting with ERβ in human lung adenocarcinoma cells that respond proliferatively to estradiol (E2) are distinct from those in non-E2-responsive cells.Methods
FLAG affinity purification of FLAG-ERβ-interacting proteins was used to isolate ERβ-interacting proteins in whole cell extracts from E2 proliferative H1793 and non-E2-proliferative A549 lung adenocarcinoma cell lines. Following trypsin digestion, proteins were identified using liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). Proteomic data were analyzed using Ingenuity Pathway Analysis. Select results were confirmed by coimmunoprecipitation.Results
LC-MS/MS identified 27 non-redundant ERβ-interacting proteins. ERβ-interacting proteins included hsp70, hsp60, vimentin, histones and calmodulin. Ingenuity Pathway Analysis of the ERβ-interacting proteins revealed differences in molecular and functional networks between H1793 and A549 lung adenocarcinoma cells. Coimmunoprecipitation experiments in these and other lung adenocarcinoma cells confirmed that ERβ and EGFR interact in a gender-dependent manner and in response to E2 or EGF. BRCA1 interacted with ERβ in A549 cell lines and in human lung adenocarcinoma tumors, but not normal lung tissue.Conclusion
Our results identify specific differences in ERβ-interacting proteins in lung adenocarcinoma cells corresponding to ligand-dependent differences in estrogenic responses.39.
Haen SP Gouttefangeas C Schmidt D Boss A Clasen S von Herbay A Kosan B Aebert H Pereira PL Rammensee HG 《Cell stress & chaperones》2011,16(5):495-504
Due to their adjuvant effect and their ability to chaperone tumor-associated peptides, heat shock proteins constitute a potent
alarm signal for the immune system and can lead to activation of anti-tumor T-cell immunity. Radiofrequency ablation has been
reported to induce heat shock protein expression especially that of heat shock protein 70 in sublethally damaged tumor cells.
In this study, we evaluated the release of heat shock protein 70 into the serum of cancer-bearing patients directly after
radiofrequency ablation. Sera of 22 patients undergoing radiofrequency ablation for the treatment of primary and secondary
malignancies of the liver, kidney, and lung, as well as control sera of 20 patients undergoing diagnostic liver biopsy were
analyzed using a manufactured heat shock protein 70 ELISA. A significant increase in serum levels of heat shock protein 70
was detectable in the patient cohort 1 day after radiofrequency ablation. More than a twofold increase was observed in nine
out of 22 patients, which tended to correlate with favorable clinical outcome. No patient of the control group revealed a
comparable increase. Radiofrequency ablation can lead to a release of heat shock protein 70 into the serum, which is transiently
detectable 1 day after treatment. Elevated heat shock protein 70 serum levels may constitute a biomarker for favorable clinical
outcome. 相似文献
40.
Sigrid NW Vorrink Helianthe SM Kort Thierry Troosters Jan-Willem J Lammers 《Respiratory research》2011,12(1):33