全文获取类型
收费全文 | 2278篇 |
免费 | 205篇 |
国内免费 | 2篇 |
专业分类
2485篇 |
出版年
2023年 | 7篇 |
2022年 | 15篇 |
2021年 | 30篇 |
2020年 | 24篇 |
2019年 | 17篇 |
2018年 | 39篇 |
2017年 | 34篇 |
2016年 | 59篇 |
2015年 | 106篇 |
2014年 | 128篇 |
2013年 | 130篇 |
2012年 | 172篇 |
2011年 | 154篇 |
2010年 | 104篇 |
2009年 | 102篇 |
2008年 | 142篇 |
2007年 | 150篇 |
2006年 | 172篇 |
2005年 | 144篇 |
2004年 | 114篇 |
2003年 | 123篇 |
2002年 | 136篇 |
2001年 | 23篇 |
2000年 | 18篇 |
1999年 | 22篇 |
1998年 | 33篇 |
1997年 | 20篇 |
1996年 | 29篇 |
1995年 | 23篇 |
1994年 | 31篇 |
1993年 | 18篇 |
1992年 | 25篇 |
1991年 | 14篇 |
1990年 | 11篇 |
1989年 | 17篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 13篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 7篇 |
1978年 | 4篇 |
1976年 | 9篇 |
1975年 | 3篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1965年 | 2篇 |
1951年 | 2篇 |
排序方式: 共有2485条查询结果,搜索用时 15 毫秒
61.
Christoph Tondera Markus Laube Christin Wimmer Torsten Kniess Birgit Mosch Kay Großmann Jens Pietzsch 《Biochemical and biophysical research communications》2013,430(1):301-306
This study aimed at visualization of cyclooxygenase-2 (COX-2) protein expression in melanoma cells by confocal laser induced cryofluorescence microscopy using 4-(3-(4-methoxyphenyl)-1H-indol-2-yl)benzene-sulfonamide (C1) representative for a novel class of autofluorescent 2,3-diarylsubstituted indole-based selective COX-2 inhibitors.COX-2 expression was measured in human melanoma cell lines A2058 and MelJuso by immunocytochemistry and immunoblotting. Cellular uptake experiments using varying C1 concentrations down to 0.1 nM (with/without molar excess of celecoxib as control) were performed at 37 °C. Cryofluorescence microscopy was conducted at 20 K.COX-2 protein expression was successfully visualized by C1 in A2058 cells. COX-2-negative MelJuso cells showed no specific accumulation of C1. Control experiments using celecoxib and, additionally, implemented fluorescence spectroscopy confirmed specificity of both cellular uptake and intracellular association of C1.Cryofluorescence microscopy in combination with spectroscopy allowed for visualization of COX-2 protein expression in melanoma cells in vitro using a selective COX-2 inhibitor at very low concentrations. 相似文献
62.
Stephen Mosher Heike Seybold Patricia Rodriguez Mark Stahl Kelli A. Davies Sajeewani Dayaratne Santiago A. Morillo Michael Wierzba Bruno Favery Harald Keller Frans E. Tax Birgit Kemmerling 《The Plant journal : for cell and molecular biology》2013,73(3):469-482
The tyrosine‐sulfated peptides PSKα and PSY1 bind to specific leucine‐rich repeat surface receptor kinases and control cell proliferation in plants. In a reverse genetic screen, we identified the phytosulfokine (PSK) receptor PSKR1 as an important component of plant defense. Multiple independent loss‐of‐function mutants in PSKR1 are more resistant to biotrophic bacteria, show enhanced pathogen‐associated molecular pattern responses and less lesion formation after infection with the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. By contrast, pskr1 mutants are more susceptible to necrotrophic fungal infection with Alternaria brassicicola, show more lesion formation and fungal growth which is not observed on wild‐type plants. The antagonistic effect on biotrophic and necrotrophic pathogen resistance is reflected by enhanced salicylate and reduced jasmonate responses in the mutants, suggesting that PSKR1 suppresses salicylate‐dependent defense responses. Detailed analysis of single and multiple mutations in the three paralogous genes PSKR1, ‐2 and PSY1‐receptor (PSY1R) determined that PSKR1 and PSY1R, but not PSKR2, have a partially redundant effect on plant immunity. In animals and plants, peptide sulfation is catalyzed by a tyrosylprotein sulfotransferase (TPST). Mutants lacking TPST show increased resistance to bacterial infection and increased susceptibility to fungal infection, mimicking the triple receptor mutant phenotypes. Feeding experiments with PSKα in tpst‐1 mutants partially restore the defense‐related phenotypes, indicating that perception of the PSKα peptide has a direct effect on plant defense. These results suggest that the PSKR subfamily integrates growth‐promoting and defense signals mediated by sulfated peptides and modulates cellular plasticity to allow flexible adjustment to environmental changes. 相似文献
63.
Thomas Heiberg Birgit Kriener Tom Tetzlaff Alex Casti Gaute T. Einevoll Hans E. Plesser 《Journal of computational neuroscience》2013,35(3):359-375
Firing-rate models provide a practical tool for studying signal processing in the early visual system, permitting more thorough mathematical analysis than spike-based models. We show here that essential response properties of relay cells in the lateral geniculate nucleus (LGN) can be captured by surprisingly simple firing-rate models consisting of a low-pass filter and a nonlinear activation function. The starting point for our analysis are two spiking neuron models based on experimental data: a spike-response model fitted to data from macaque (Carandini et al. J. Vis., 20(14), 1–2011, 2007), and a model with conductance-based synapses and afterhyperpolarizing currents fitted to data from cat (Casti et al. J. Comput. Neurosci., 24(2), 235–252, 2008). We obtained the nonlinear activation function by stimulating the model neurons with stationary stochastic spike trains, while we characterized the linear filter by fitting a low-pass filter to responses to sinusoidally modulated stochastic spike trains. To account for the non-Poisson nature of retinal spike trains, we performed all analyses with spike trains with higher-order gamma statistics in addition to Poissonian spike trains. Interestingly, the properties of the low-pass filter depend only on the average input rate, but not on the modulation depth of sinusoidally modulated input. Thus, the response properties of our model are fully specified by just three parameters (low-frequency gain, cutoff frequency, and delay) for a given mean input rate and input regularity. This simple firing-rate model reproduces the response of spiking neurons to a step in input rate very well for Poissonian as well as for non-Poissonian input. We also found that the cutoff frequencies, and thus the filter time constants, of the rate-based model are unrelated to the membrane time constants of the underlying spiking models, in agreement with similar observations for simpler models. 相似文献
64.
Arwyn Edwards Brian Douglas Alexandre M. Anesio Sara M. Rassner Tristram D.L. Irvine-Fynn Birgit Sattler Gareth W. Griffith 《Fungal Ecology》2013,6(2):168-176
Cryoconite holes on glacier surfaces are ice-cold hot spots of microbial diversity and activity but still little is known about their fungal inhabitants. We provide the first report of distinctive fungal communities in cryoconite debris from three valley glaciers at Kongsfjorden, Svalbard. Multivariate analysis of terminal-restriction fragment length polymorphism (T-RFLP) profiles of rRNA ITS amplicons revealed that quite distinct fungal communities were found in cryoconite holes compared with soils from adjacent moraine and tundra sites, and that communities on glaciers with contrasting ice-surface hydrology also differed. Most of the fungi cultured from cryoconite sediment were basidiomycetous yeasts or filamentous Ascomycota (Helotiales/Pleosporales). The latter included aeroaquatic fungi, such as Articulospora and Varicosporium, implying a role for these important freshwater decomposers in the carbon dynamics of cryoconite holes. Matching of the dominant peaks from T-RFLP analysis to predicted peaks of cultured isolates confirmed the abundance of these aeroaquatic fungi but also revealed that most of the dominant T-RFLP peaks did not match any cultured isolates. Considering the prevalence and endangerment of glacial environments worldwide, these findings would suggest that their potential as reservoirs of fungal diversity should not be overlooked. 相似文献
65.
Joleen Masschelein Wesley Mattheus Ling-Jie Gao Pieter Moons Rob Van Houdt Birgit Uytterhoeven Chris Lamberigts Eveline Lescrinier Jef Rozenski Piet Herdewijn Abram Aertsen Chris Michiels Rob Lavigne 《PloS one》2013,8(1)
Serratia plymuthica strain RVH1, initially isolated from an industrial food processing environment, displays potent antimicrobial activity towards a broad spectrum of Gram-positive and Gram-negative bacterial pathogens. Isolation and subsequent structure determination of bioactive molecules led to the identification of two polyamino antibiotics with the same molecular structure as zeamine and zeamine II as well as a third, closely related analogue, designated zeamine I. The gene cluster encoding the biosynthesis of the zeamine antibiotics was cloned and sequenced and shown to encode FAS, PKS as well as NRPS related enzymes in addition to putative tailoring and export enzymes. Interestingly, several genes show strong homology to the pfa cluster of genes involved in the biosynthesis of long chain polyunsaturated fatty acids in marine bacteria. We postulate that a mixed FAS/PKS and a hybrid NRPS/PKS assembly line each synthesize parts of the backbone that are linked together post-assembly in the case of zeamine and zeamine I. This interaction reflects a unique interplay between secondary lipid and secondary metabolite biosynthesis. Most likely, the zeamine antibiotics are produced as prodrugs that undergo activation in which a nonribosomal peptide sequence is cleaved off. 相似文献
66.
Tomá? Venit Rastislav Dzijak Al?běta Kalendová Michal Kahle Jana Roho?ková Volker Schmidt Thomas Rülicke Birgit Rathkolb Wolfgang Hans Alexander Bohla Oliver Eickelberg Tobias Stoeger Eckhard Wolf Ali ?nder Yildirim Valérie Gailus-Durner Helmut Fuchs Martin Hrabě de Angelis Pavel Hozák 《PloS one》2013,8(4)
67.
The chicken leukocyte receptor complex located on microchromosome 31 encodes the chicken Ig-like receptors (CHIR), a vastly expanded gene family which can be further divided into three subgroups: activating CHIR-A, bifunctional CHIR-AB and inhibitory CHIR-B. Here, we investigated the presence of CHIR homologues in other bird species. The available genome databases of turkey, duck and zebra finch were screened with different strategies including BLAST searches employing various CHIR sequences, and keyword searches. We could not identify CHIR homologues in the distantly related zebra finch and duck, however, several partial and complete sequences of CHIR homologues were identified on chromosome 3 of the turkey genome. They were designated as turkey Ig-like receptors (TILR). Using cDNA derived from turkey blood and spleen RNA, six full length TILR could be amplified and further divided according to the typical sequence features into one activating TILR-A, one inhibitory TILR-B and four bifunctional TILR-AB. Since the TILR-AB sequences all displayed the critical residues shown to be involved in binding to IgY, we next confirmed the IgY binding using a soluble TILR-AB1-huIg fusion protein. This fusion protein reacted with IgY derived from various gallinaceous birds, but not with IgY from other bird species. Finally, we tested various mab directed against CHIR for their crossreactivity with either turkey or duck leukocytes. Whereas no staining was detectable with duck cells, the CHIR-AB1 specific mab 8D12 and the CHIR-A2 specific mab 13E2 both reacted with a leukocyte subpopulation that was further identified as thrombocytes by double immunofluorescence employing B-cell, T-cell and thrombocyte specific reagents. In summary, although the turkey harbors similar LRC genes as the chicken, their distribution seems to be distinct with predominance on thrombocytes rather than lymphocytes. 相似文献
68.
Birgit Adam Isabell Klawonn Jennie B Svedén Johanna Bergkvist Nurun Nahar Jakob Walve Sten Littmann Martin J Whitehouse Gaute Lavik Marcel M M Kuypers Helle Ploug 《The ISME journal》2016,10(2):450-459
We investigated the role of N2-fixation by the colony-forming cyanobacterium, Aphanizomenon spp., for the plankton community and N-budget of the N-limited Baltic Sea during summer by using stable isotope tracers combined with novel secondary ion mass spectrometry, conventional mass spectrometry and nutrient analysis. When incubated with 15N2, Aphanizomenon spp. showed a strong 15N-enrichment implying substantial 15N2-fixation. Intriguingly, Aphanizomenon did not assimilate tracers of 15NH4+ from the surrounding water. These findings are in line with model calculations that confirmed a negligible N-source by diffusion-limited NH4+ fluxes to Aphanizomenon colonies at low bulk concentrations (<250 nm) as compared with N2-fixation within colonies. No N2-fixation was detected in autotrophic microorganisms <5 μm, which relied on NH4+ uptake from the surrounding water. Aphanizomenon released about 50% of its newly fixed N2 as NH4+. However, NH4+ did not accumulate in the water but was transferred to heterotrophic and autotrophic microorganisms as well as to diatoms (Chaetoceros sp.) and copepods with a turnover time of ~5 h. We provide direct quantitative evidence that colony-forming Aphanizomenon releases about half of its recently fixed N2 as NH4+, which is transferred to the prokaryotic and eukaryotic plankton forming the basis of the food web in the plankton community. Transfer of newly fixed nitrogen to diatoms and copepods furthermore implies a fast export to shallow sediments via fast-sinking fecal pellets and aggregates. Hence, N2-fixing colony-forming cyanobacteria can have profound impact on ecosystem productivity and biogeochemical processes at shorter time scales (hours to days) than previously thought. 相似文献
69.
There is extensive evidence for an association between an attentional bias towards emotionally negative stimuli and vulnerability to stress-related psychopathology. Less is known about whether selective attention towards emotionally positive stimuli relates to mental health and stress resilience. The current study used a modified Dot Probe task to investigate if individual differences in attentional biases towards either happy or angry emotional stimuli, or an interaction between these biases, are related to self-reported trait stress resilience. In a nonclinical sample (N = 43), we indexed attentional biases as individual differences in reaction time for stimuli preceded by either happy or angry (compared to neutral) face stimuli. Participants with greater attentional bias towards happy faces (but not angry faces) reported higher trait resilience. However, an attentional bias towards angry stimuli moderated this effect: The attentional bias towards happy faces was only predictive for resilience in those individuals who also endorsed an attentional bias towards angry stimuli. An attentional bias towards positive emotional stimuli may thus be a protective factor contributing to stress resilience, specifically in those individuals who also endorse an attentional bias towards negative emotional stimuli. Our findings therefore suggest a novel target for prevention and treatment interventions addressing stress-related psychopathology. 相似文献
70.
Ecological community patterns are often extremely complex and the factors with the greatest influence on community structure have yet to be identified. In this study we used the elements of metacommunity structure (EMS) framework to characterize the metacommunities of freshwater nematodes in 16 European lakes at four geographical scales (radius ranging from 80 m to 360 km). The site characteristics associated with site scores indicative of the structuring gradient were identified using Spearman rank correlations. The metacommunities of the 174 nematode species included in this analysis mostly had a coherent pattern. The degree of turnover increased with increasing scale. Ordination scores correlated with geographical variables on the larger scales and with the trophic state index on a regional scale. The association of the structuring gradient with spatial variables and the scale-dependent increase in turnover showed that nematode dispersal was limited. The different metacommunity patterns identified at the increasing geographical scales suggested different, scale-related mechanisms of species distribution, with species sorting dominating on smaller and mass effects on larger geographical scales. 相似文献