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71.
Peng Lin Sarah M. Hartz Zhehao Zhang Scott F. Saccone Jia Wang Jay A. Tischfield Howard J. Edenberg John R. Kramer Alison M.Goate Laura J. Bierut John P. Rice for the COGA Collaborators COGEND Collaborators GENEVA 《PloS one》2010,5(3)
Background
As the amount of data from genome wide association studies grows dramatically, many interesting scientific questions require imputation to combine or expand datasets. However, there are two situations for which imputation has been problematic: (1) polymorphisms with low minor allele frequency (MAF), and (2) datasets where subjects are genotyped on different platforms. Traditional measures of imputation cannot effectively address these problems.Methodology/Principal Findings
We introduce a new statistic, the imputation quality score (IQS). In order to differentiate between well-imputed and poorly-imputed single nucleotide polymorphisms (SNPs), IQS adjusts the concordance between imputed and genotyped SNPs for chance. We first evaluated IQS in relation to minor allele frequency. Using a sample of subjects genotyped on the Illumina 1 M array, we extracted those SNPs that were also on the Illumina 550 K array and imputed them to the full set of the 1 M SNPs. As expected, the average IQS value drops dramatically with a decrease in minor allele frequency, indicating that IQS appropriately adjusts for minor allele frequency. We then evaluated whether IQS can filter poorly-imputed SNPs in situations where cases and controls are genotyped on different platforms. Randomly dividing the data into “cases” and “controls”, we extracted the Illumina 550 K SNPs from the cases and imputed the remaining Illumina 1 M SNPs. The initial Q-Q plot for the test of association between cases and controls was grossly distorted (λ = 1.15) and had 4016 false positives, reflecting imputation error. After filtering out SNPs with IQS<0.9, the Q-Q plot was acceptable and there were no longer false positives. We then evaluated the robustness of IQS computed independently on the two halves of the data. In both European Americans and African Americans the correlation was >0.99 demonstrating that a database of IQS values from common imputations could be used as an effective filter to combine data genotyped on different platforms.Conclusions/Significance
IQS effectively differentiates well-imputed and poorly-imputed SNPs. It is particularly useful for SNPs with low minor allele frequency and when datasets are genotyped on different platforms. 相似文献72.
Gap Dynamics in a Seagrass Landscape 总被引:2,自引:0,他引:2
We investigated gap dynamics within a shallow subtidal landscape characterized by seagrass vegetation and examined the relationship
between gap formation and selected physical factors. The study was conducted over 2 y by using a biannual mapping of seagrass
and water depth across an 48,800-m2 area in Tampa Bay, Florida. In addition, monthly sediment deposition or erosion was recorded at 96 locations within the landscape.
Gaps represented from 2.4% to 5.7% of the seagrass landscape, and all were within monospecific stands of Halodule wrightii. Gaps ranged in size from 10 to 305 m2 and most frequently decreased in size over time. Most gaps were small and short lived (less than 6-mo duration), but the
second age group most frequently recorded was at least 1.5 y old. No new species of seagrass invaded the gaps with Halodule replacing itself 100% of the time. Gaps were recorded over the entire range of water depths within the landscape. Neither
gap area nor persistence of gaps was related to water depth. However gap area was associated positively with the number of
extreme sedimentation events. Gaps originated not only from removal of interior vegetation (similar to classic gaps) but also
from differential growth of the seagrass margin (similar to edaphic gaps). Distinct seasonal components to the mode of formation
were detected with interior-produced gaps originating primarily in the winter and margin gaps most commonly during summer.
These results combine to illustrate the importance of large-scale studies with fine-scale resolution for deciphering unique
features of seagrass landscape dynamics. Our historical information suggests that a static enumeration of gaps may not provide
an accurate assessment of disturbance intensity in this system, and the seagrass mosaic probably is explained best by a combination
of disturbance regimes and edaphic factors, such as sediment stability. Moreover, we suggest that even in areas characterized
by monospecific stands of vegetation and over short or moderate time periods, gaps indirectly may influence community structure
and ecosystem function via modification of habitat arrangement.
Received 17 September 1998; accepted 26 April 1999. 相似文献
73.
74.
Genome-wide evaluation of histone methylation changes associated with leaf senescence in Arabidopsis
Brusslan JA Rus Alvarez-Canterbury AM Nair NU Rice JC Hitchler MJ Pellegrini M 《PloS one》2012,7(3):e33151
Leaf senescence is the orderly dismantling of older tissue that allows recycling of nutrients to developing portions of the plant and is accompanied by major changes in gene expression. Histone modifications correlate to levels of gene expression, and this study utilizes ChIP-seq to classify activating H3K4me3 and silencing H3K27me3 marks on a genome-wide scale for soil-grown mature and naturally senescent Arabidopsis leaves. ChIPnorm was used to normalize data sets and identify genomic regions with significant differences in the two histone methylation patterns, and the differences were correlated to changes in gene expression. Genes that showed an increase in the H3K4me3 mark in older leaves were senescence up-regulated, while genes that showed a decrease in the H3K4me3 mark in the older leaves were senescence down-regulated. For the H3K27me3 modification, genes that lost the H3K27me3 mark in older tissue were senescence up-regulated. Only a small number of genes gained the H3K27me3 mark, and these were senescence down-regulated. Approximately 50% of senescence up-regulated genes lacked the H3K4me3 mark in both mature and senescent leaf tissue. Two of these genes, SAG12 and At1g73220, display strong senescence up-regulation without the activating H3K4me3 histone modification. This study provides an initial epigenetic framework for the developmental transition into senescence. 相似文献
75.
Karan J. Odom Marcelo Araya-Salas Janelle L. Morano Russell A. Ligon Gavin M. Leighton Conor C. Taff Anastasia H. Dalziell Alexis C. Billings Ryan R. Germain Michael Pardo Luciana Guimarães de Andrade Daniela Hedwig Sara C. Keen Yu Shiu Russell A. Charif Michael S. Webster Aaron N. Rice 《Biological reviews of the Cambridge Philosophical Society》2021,96(4):1135-1159
Animals produce a wide array of sounds with highly variable acoustic structures. It is possible to understand the causes and consequences of this variation across taxa with phylogenetic comparative analyses. Acoustic and evolutionary analyses are rapidly increasing in sophistication such that choosing appropriate acoustic and evolutionary approaches is increasingly difficult. However, the correct choice of analysis can have profound effects on output and evolutionary inferences. Here, we identify and address some of the challenges for this growing field by providing a roadmap for quantifying and comparing sound in a phylogenetic context for researchers with a broad range of scientific backgrounds. Sound, as a continuous, multidimensional trait can be particularly challenging to measure because it can be hard to identify variables that can be compared across taxa and it is also no small feat to process and analyse the resulting high-dimensional acoustic data using approaches that are appropriate for subsequent evolutionary analysis. Additionally, terminological inconsistencies and the role of learning in the development of acoustic traits need to be considered. Phylogenetic comparative analyses also have their own sets of caveats to consider. We provide a set of recommendations for delimiting acoustic signals into discrete, comparable acoustic units. We also present a three-stage workflow for extracting relevant acoustic data, including options for multivariate analyses and dimensionality reduction that is compatible with phylogenetic comparative analysis. We then summarize available phylogenetic comparative approaches and how they have been used in comparative bioacoustics, and address the limitations of comparative analyses with behavioural data. Lastly, we recommend how to apply these methods to acoustic data across a range of study systems. In this way, we provide an integrated framework to aid in quantitative analysis of cross-taxa variation in animal sounds for comparative phylogenetic analysis. In addition, we advocate the standardization of acoustic terminology across disciplines and taxa, adoption of automated methods for acoustic feature extraction, and establishment of strong data archival practices for acoustic recordings and data analyses. Combining such practices with our proposed workflow will greatly advance the reproducibility, biological interpretation, and longevity of comparative bioacoustic studies. 相似文献
76.
Gary R Hunter Bradley R Newcomer Roland L Weinsier Daniel L Karapondo D Enette Larson-Meyer Denis R Joanisse Marcas M Bamman 《Journal of applied physiology》2002,93(1):70-76
The purpose of this study was to determine whether muscle metabolic capacity was inversely related to age after adjusting for physical activity in sedentary premenopausal women. Eighty-three women (ages 23-47 yr) had their free-living, activity-related energy expenditure evaluated with doubly labeled water procedures, and room calorimeter determined sleeping energy expenditure. Maximum O(2) uptake and strength were evaluated in all subjects, whereas 31P-magnetic resonance spectroscopy determined metabolic economy during maximal exercise, and muscle biopsy maximal enzyme activity was evaluated in subsets of the sample (48 and 18 subjects, respectively). Age was significantly related to whole body treadmill endurance time (r = -0.32), plantar flexion strength (r = -0.29), maximum O(2) uptake (r = -0.27), (31)P-magnetic resonance spectroscopy ADP recovery rate (r = -0.44), and anaerobic glycolytic capacity (r = -0.37), and muscle biopsy citrate synthase activity (r = -0.48), glyceraldehyde-3-phosphate dehydrogenase (r = -0.54), phosphofructokinase (r = -0.62), and phosphorylase (r = -0.58) activity even after adjusting for activity-related energy expenditure. These data suggest that, in sedentary premenopausal women, both oxidative and glycolytic muscle capacity decrease with age even when physical activity is taken into account. 相似文献
77.
Summary Nitrogen fixation in the natural, Agropyron-Koeleria grassland ecosystem was studied using the C2H2-C2H4 and N15 assays. Small soil samples and also undisturbed soil cores were used for analyses. Both techniques indicated that grassland
and associated cultivated soils had low fixation rates (0.6–1.8 kg/ha per 28 days in the laboratory and, 1 kg/ha per season
under actual field conditions). Algal colonies (Nostoc spp.) on the soil surface were active fixers when the surface of the grassland was moist. However, their small biomass limits
the extent of fixation in most areas.
In native grassland, 16 legumes bore nodules. The three most common speciesVicia americana, Thermopsis rhombifolia andOxytropis sericea, all of which had active nodules, contributed 10 per cent of the total nitrogenase activity.
The non-legumesElaeagnus commutata andShepherdia argentea were profusely nodulated with active nodules, but were confined to specific habitats. No nodules were found onArtemisia orOpuntia spp.
The major, heterotrophic, asymbiotic bacteria in the soil were clostridia. These utilize substrates produced by aerobic cellulose
and hemicellulose degrading organisms to fix N in anaerobic microsites. The C2H2:N2 reduction ratio was 3 to 1 in large, aerobic core samples, but was greater under water-logged conditions where high fixation
rates occurred. 相似文献
78.
Justin M. Bradley Dimitry A. Svistunenko Michael T. Wilson Andrew M. Hemmings Geoffrey R. Moore Nick E. Le Brun 《The Journal of biological chemistry》2020,295(51):17602
Iron is an essential micronutrient, and, in the case of bacteria, its availability is commonly a growth-limiting factor. However, correct functioning of cells requires that the labile pool of chelatable “free” iron be tightly regulated. Correct metalation of proteins requiring iron as a cofactor demands that such a readily accessible source of iron exist, but overaccumulation results in an oxidative burden that, if unchecked, would lead to cell death. The toxicity of iron stems from its potential to catalyze formation of reactive oxygen species that, in addition to causing damage to biological molecules, can also lead to the formation of reactive nitrogen species. To avoid iron-mediated oxidative stress, bacteria utilize iron-dependent global regulators to sense the iron status of the cell and regulate the expression of proteins involved in the acquisition, storage, and efflux of iron accordingly. Here, we survey the current understanding of the structure and mechanism of the important members of each of these classes of protein. Diversity in the details of iron homeostasis mechanisms reflect the differing nutritional stresses resulting from the wide variety of ecological niches that bacteria inhabit. However, in this review, we seek to highlight the similarities of iron homeostasis between different bacteria, while acknowledging important variations. In this way, we hope to illustrate how bacteria have evolved common approaches to overcome the dual problems of the insolubility and potential toxicity of iron. 相似文献
79.
Chavda S Liu Y Babu B Davis R Sielaff A Ruprich J Westrate L Tronrud C Ferguson A Franks A Tzou S Adkins C Rice T Mackay H Kluza J Tahir SA Lin S Kiakos K Bruce CD Wilson WD Hartley JA Lee M 《Biochemistry》2011,50(15):3127-3136
With the aim of incorporating a recognition element that acts as a fluorescent probe upon binding to DNA, three novel pyrrole (P) and imidazole (I)-containing polyamides were synthesized. The compounds contain a p-anisylbenzimidazolecarboxamido (Hx) moiety attached to a PP, IP, or PI unit, giving compounds HxPP (2), HxIP (3), and HxPI (4), respectively. These fluorescent hybrids were tested against their complementary nonfluorescent, non-formamido tetraamide counterparts, namely, PPPP (5), PPIP (6), and PPPI (7) (cognate sequences 5'-AAATTT-3', 5'-ATCGAT-3', and 5'-ACATGT-3', respectively). The binding affinities for both series of polyamides for their cognate and noncognate sequences were ascertained by surface plasmon resonance (SPR) studies, which revealed that the Hx-containing polyamides gave binding constants in the 10(6) M(-1) range while little binding was observed for the noncognates. The binding data were further compared to the corresponding and previously reported formamido-triamides f-PPP (8), f-PIP (9), and f-PPI (10). DNase I footprinting studies provided additional evidence that the Hx moiety behaved similarly to two consecutive pyrroles (PP found in 5-7), which also behaved like a formamido-pyrrole (f-P) unit found in distamycin and many formamido-triamides, including 8-10. The biophysical characterization of polyamides 2-7 on their binding to the abovementioned DNA sequences was determined using thermal melts (ΔT(M)), circular dichroism (CD), and isothermal titration calorimetry (ITC) studies. Density functional calculations (B3LYP) provided a theoretical framework that explains the similarity between PP and Hx on the basis of molecular electrostatic surfaces and dipole moments. Furthermore, emission studies on polyamides 2 and 3 showed that upon excitation at 322 nm binding to their respective cognate sequences resulted in an increase in fluorescence at 370 nm. These low molecular weight polyamides show promise for use as probes for monitoring DNA recognition processes in cells. 相似文献
80.