全文获取类型
收费全文 | 93504篇 |
免费 | 305篇 |
国内免费 | 881篇 |
专业分类
94690篇 |
出版年
2023年 | 11篇 |
2022年 | 23篇 |
2021年 | 27篇 |
2020年 | 49篇 |
2019年 | 70篇 |
2018年 | 11868篇 |
2017年 | 10694篇 |
2016年 | 7462篇 |
2015年 | 615篇 |
2014年 | 312篇 |
2013年 | 338篇 |
2012年 | 4237篇 |
2011年 | 12819篇 |
2010年 | 11997篇 |
2009年 | 8234篇 |
2008年 | 9790篇 |
2007年 | 11363篇 |
2006年 | 258篇 |
2005年 | 507篇 |
2004年 | 960篇 |
2003年 | 1019篇 |
2002年 | 780篇 |
2001年 | 255篇 |
2000年 | 161篇 |
1999年 | 26篇 |
1998年 | 11篇 |
1997年 | 22篇 |
1996年 | 9篇 |
1995年 | 2篇 |
1994年 | 6篇 |
1993年 | 29篇 |
1992年 | 20篇 |
1991年 | 41篇 |
1990年 | 9篇 |
1989年 | 7篇 |
1988年 | 18篇 |
1987年 | 13篇 |
1984年 | 7篇 |
1983年 | 18篇 |
1982年 | 2篇 |
1979年 | 2篇 |
1975年 | 5篇 |
1972年 | 246篇 |
1971年 | 274篇 |
1970年 | 5篇 |
1965年 | 13篇 |
1962年 | 24篇 |
1956年 | 5篇 |
1944年 | 12篇 |
1940年 | 10篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
211.
Sarah A. Cocherell Stephanie N. Chun Dennis E. Cocherell Lisa C. Thompson A. Peter Klimley Joseph J. CechJr. 《Environmental Biology of Fishes》2012,93(1):143-150
In regulated rivers, fluctuating water depths associated with pulsed discharges may strand small fish in side channels and
pools. Quantitative assessments of stranded fish are difficult in field studies (e.g., due to unknown effects of avian and
terrestrial vertebrate predators). To assess such lateral displacement and stranding on juvenile stream fishes, we designed,
constructed, and tested (with three species) a 2 × 1-m, lateral-displacement flume. The flume featured a main channel that
never drained and a raised, wide “floodplain” channel that alternately flooded, with a simulated pulse, and became dewatered.
The floodplain contained four pools, with different shapes and draining capacities, in which fish could become stranded as
the water level subsided. Fish-stranding rates (8%) in this relatively compact laboratory flume, after exposure to simulated
pulsed stream flows, were comparable to those observed in past investigations using larger, artificial streams. 相似文献
212.
Torre J. Hovick Brady W. Allred Devan A. McGranahan Michael W. Palmer R. Dwayne Elmore Samuel D. Fuhlendorf 《Biodiversity and Conservation》2016,25(2):345-356
A species distribution combines the resources and climatic tolerances that allow an individual or population to persist. As these conditions change, one mechanism to maintain favorable resources is for an organism to shift its range. Much of the research examining range shifts has focused on dynamic distribution boundaries wheras the role of species breeding habitat or migration strategies on shift tendencies has received less attention. We expand on previous research by using a large suite of avian species (i.e., 277), analyzing observed abundance-weighted average latitudes, and categorizing species by breeding environment and migration strategy. We used the North American Breeding Bird Survey dataset to address two questions: (1) Has the center of observed abundance for individual species shifted latitudinally? (2) Is there a relationship between migration strategy or breeding habitat and range shifts? Results indicate the majority of species have experienced poleward range shifts over the last 43 years, and birds breeding in all habitat showed trends of poleward shift but only those species breeding in scrub-shrub and grassland environments were different from zero. Additionally, species that are short distance migrants are experiencing significant poleward shifts while Neotropical and permanent residents had shifts that were not different from zero. Our findings do support the general trend expected from climate driven changes (i.e., > 52 % shifting poleward), however, the proportion of species exhibiting equatorial shifts (24 %) or no significant shifts (23 %) illustrates the complex interplay between land cover, climate, species interactions, and other forces that can interact to influence breeding ranges over time. Regardless of the mechanisms driving range shifts, our findings emphasize the need for connecting and expanding habitats for those species experiencing range shifts. This research describes the patterns of breeding birds through central North America and we encourage future research to focus on the mechanisms driving these patterns. 相似文献
213.
Targeting cleavage and polyadenylation specific factor 1 via shRNA inhibits cell proliferation in human ovarian cancer 总被引:1,自引:0,他引:1
Cleavage and polyadenylation specificity factor 1 (CPSF1), a member of CPSF complex, has been reported to play a key role in pre-mRNA 3′-end formation, but its possible role in ovarian cancer remains unclear. In the present study, we found the mRNA level of CPSF1 was overexpressed in ovarian cancer tissues using Oncomine Cancer Microarray database. Then the loss-of-function assays, including CCK-8, colony formation and flow cytometry assays, were performed to determine the effects of CPSF1 on cell viability, proliferation, cell cycle and apoptosis of human ovarian cancer cell lines (SKOV-3 and OVCAR-3). The results indicated that depletion of CPSF1 suppressed cell viability, impaired colony formation ability, induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis in ovarian cancer cells. Furthermore, knockdown of CPSF1 upregulated the expression of cleaved caspase-3 and PARP and downregulated CDK4/cyclin D1 expression. These data suggested that CPSF1 could promote ovarian cancer cell growth and proliferation in vitro and its depletion might serve as a potential therapeutic target for human ovarian cancer. 相似文献
214.
Syeda Mehpara Farhat Aamra Mahboob Ghazala Iqbal Touqeer Ahmed 《Biological trace element research》2017,177(1):115-121
Aluminum is associated with etiology of many neurodegenerative diseases specially Alzheimer’s disease. Chronic exposure to aluminum via drinking water results in aluminum deposition in the brain that leads to cognitive deficits. The study aimed to determine the effects of aluminum on cholinergic biomarkers, i.e., acetylcholine level, free choline level, and choline acetyltransferase gene expression, and how cholinergic deficit affects novel object recognition and sociability in mice. Mice were treated with AlCl3 (250 mg/kg). Acetylcholine level, free choline level, and choline acetyltransferase gene expression were determined in cortex, hippocampus, and amygdala. The mice were subjected to behavior tests (novel object recognition and social novelty preference) to assess memory deficits. The acetylcholine level in cortex and hippocampus was significantly reduced in aluminum-treated animals, as compared to cortex and hippocampus of control animals. Acetylcholine level in amygdala of aluminum-treated animals remained unchanged. Free choline level in all the three brain parts was found unaltered in aluminum-treated mice. The novel object recognition memory was severely impaired in aluminum-treated mice, as compared to the control group. Similarly, animals treated with aluminum showed reduced sociability compared to the control mice group. Our study demonstrates that aluminum exposure via drinking water causes reduced acetylcholine synthesis in spite of normal free choline availability. This deficit is caused by reduced recycling of acetylcholine due to lower choline acetyltransferase level. This cholinergic hypofunction leads to cognitive and memory deficits. Moreover, hippocampus is the most affected brain part after aluminum intoxication. 相似文献
215.
Identification of suitable endogenous control genes for microRNA gene expression analysis in human breast cancer 总被引:2,自引:0,他引:2
Pamela A Davoren Roisin E McNeill Aoife J Lowery Michael J Kerin Nicola Miller 《BMC molecular biology》2008,9(1):76
The discovery of microRNAs (miRNAs) added an extra level of intricacy to the already complex system regulating gene expression.
These single-stranded RNA molecules, 18–25 nucleotides in length, negatively regulate gene expression through translational
inhibition or mRNA cleavage. The discovery that aberrant expression of specific miRNAs contributes to human disease has fueled
much interest in profiling the expression of these molecules. Real-time quantitative PCR (RQ-PCR) is a sensitive and reproducible
gene expression quantitation technique which is now being used to profile miRNA expression in cells and tissues. To correct
for systematic variables such as amount of starting template, RNA quality and enzymatic efficiencies, RQ-PCR data is commonly
normalised to an endogenous control (EC) gene, which ideally, is stably-expressed across the test sample set. A universal
endogenous control suitable for every tissue type, treatment and disease stage has not been identified and is unlikely to
exist, so, to avoid introducing further error in the quantification of expression data it is necessary that candidate ECs
be validated in the samples of interest. While ECs have been validated for quantification of mRNA expression in various experimental
settings, to date there is no report of the validation of miRNA ECs for expression profiling in breast tissue. In this study,
the expression of five miRNA genes (let-7a, miR-10b, miR-16, miR-21 and miR-26b) and three small nucleolar RNA genes (RNU19, RNU48 and Z30) was examined across malignant, benign and normal breast tissues to determine the most appropriate normalisation strategy.
This is the first study to identify reliable ECs for analysis of miRNA by RQ-PCR in human breast tissue. 相似文献
216.
Linda H Münger Mar Garcia-Aloy Rosa Vázquez-Fresno Doreen Gille Albert Remus R Rosana Anna Passerini María-Trinidad Soria-Florido Grégory Pimentel Tanvir Sajed David S Wishart Cristina Andres Lacueva Guy Vergères Giulia Praticò 《Genes & nutrition》2018,13(1):26
Dairy and egg products constitute an important part of Western diets as they represent an excellent source of high-quality proteins, vitamins, minerals and fats. Dairy and egg products are highly diverse and their associations with a range of nutritional and health outcomes are therefore heterogeneous. Such associations are also often weak or debated due to the difficulty in establishing correct assessments of dietary intake. Therefore, in order to better characterize associations between the consumption of these foods and health outcomes, it is important to identify reliable biomarkers of their intake. Biomarkers of food intake (BFIs) provide an accurate measure of intake, which is independent of the memory and sincerity of the subjects as well as of their knowledge about the consumed foods. We have, therefore, conducted a systematic search of the scientific literature to evaluate the current status of potential BFIs for dairy products and BFIs for egg products commonly consumed in Europe. Strikingly, only a limited number of compounds have been reported as markers for the intake of these products and none of them have been sufficiently validated. A series of challenges hinders the identification and validation of BFI for dairy and egg products, in particular, the heterogeneous composition of these foods and the lack of specificity of the markers identified so far. Further studies are, therefore, necessary to validate these compounds and to discover new candidate BFIs. Untargeted metabolomic strategies may allow the identification of novel biomarkers, which, when taken separately or in combination, could be used to assess the intake of dairy and egg products. 相似文献
217.
The reserves of fossil-based fuels, which currently seem sufficient to meet the global demands, is inevitably on the verge of exhaustion. Contemporary raw material for alternate fuel like biodiesel is usually edible plant commodity oils, whose increasing public consumption rate raises the need of finding a non-edible and fungible alternate oil source. In this quest, single cell oils (SCO) from oleaginous yeasts and fungi can provide a sustainable alternate of not only functional but also valuable (polyunsaturated fatty acids (PUFA)-rich) lipids. Researches are been increasingly driven towards increasing the SCO yield in order to realize its commercial importance. However, bulk requirement of expensive synthetic carbon substrate, which inflates the overall SCO production cost, is the major limitation towards complete acceptance of this technology. Even though substrate cost minimization could make the SCO production profitable is uncertain, it is still essential to identify suitable cheap and abundant substrates in an attempt to potentially reduce the overall process economy. One of the most sought-after in-expensive carbon reservoirs, agro-industrial wastes, can be an attractive replacement to expensive synthetic carbon substrates in this regard. The present review assess these possibilities referring to the current experimental investigations on oleaginous yeasts, and fungi reported for conversion of agro-industrial feedstocks into triacylglycerols (TAGs) and PUFA-rich lipids. Multiple associated factors regulating lipid accumulation utilizing such substrates and impeding challenges has been analyzed. The review infers that production of bulk oil in combination to high-value fatty acids, co-production strategies for SCO and different microbial metabolites, and reutilization and value addition to spent wastes could possibly leverage the high operating costs and help in commencing a successful biorefinery. Rigorous research is nevertheless required whether it is PUFA-rich oil production (for competing with algal omega oils) or neutral bulk oil production (for overcoming yield limitations and managing process economy) to establish this potential source as future resource. 相似文献
218.
Han Hu Kshitij Khatri Joshua Klein Nancy Leymarie Joseph Zaia 《Glycoconjugate journal》2016,33(3):285-296
Despite the publication of several software tools for analysis of glycopeptide tandem mass spectra, there remains a lack of consensus regarding the most effective and appropriate methods. In part, this reflects problems with applying standard methods for proteomics database searching and false discovery rate calculation. While the analysis of small post-translational modifications (PTMs) may be regarded as an extension of proteomics database searching, glycosylation requires specialized approaches. This is because glycans are large and heterogeneous by nature, causing glycopeptides to exist as multiple glycosylated variants. Thus, the mass of the peptide cannot be calculated directly from that of the intact glycopeptide. In addition, the chemical nature of the glycan strongly influences product ion patterns observed for glycopeptides. As a result, glycopeptidomics requires specialized bioinformatics methods. We summarize the recent progress towards a consensus for effective glycopeptide tandem mass spectrometric analysis. 相似文献
219.
Silin Wu Ye Gu Yuying Huang Tyh-Chai Wong Hailin Ding Tengfei Liu Yu Zhang Xiaobiao Zhang 《Biochemical genetics》2017,55(3):253-267
The microRNAs (miRNAs) are involved in multiple pathological processes among various types of tumors. However, the functions of miRNAs in benign brain tumors are largely unexplored. In order to explore the pathogenesis of the invasiveness in non-functional pituitary adenoma (NFPA), the miRNAs expression profile was analyzed between invasive and non-invasive non-functional pituitary adenoma by miRNAs microarray. Six most significant differentially expressed miRNAs were identified including four upregulated miRNAs hsa-miR-181b-5p, hsa-miR-181d, hsa-miR-191-3p, and hsa-miR-598 and two downregulated miRNAs hsa-miR-3676-5p and hsa-miR-383. The functions and corresponding signaling pathways of differentially expressed miRNAs were investigated by bioinformatics techniques, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The result of GO analysis indicates regulation of voltage-gated potassium channel activity, positive regulation of sodium ion transport, positive regulation of GTPase activity, negative regulation of Notch signaling pathway, etc. KEGG pathway reveals a series of biological processes, including prolactin signaling pathway, endocrine and other factor-regulated calcium reabsorption, fatty acid metabolism, neuroactive ligand-receptor interaction, etc. The miRNAs hsa-miR-181a-5p was verified by quantitative real-time PCR, and the expression level was in accordance with the microarray result. Our result can provide the evidence on featured miRNAs which play a prominent role in pituitary adenoma as effective biomarkers and therapeutic targets in the future. 相似文献
220.
Benjamin L. VaughanJr. Bryan G. Smith David L. Chopp 《Bulletin of mathematical biology》2010,72(5):1143-1165
In this paper, we study quorum sensing in Pseudomonas aeruginosa biofilms. Quorum sensing is a process where bacteria monitor their population density through the release of extra-cellular
signalling molecules. The presence of these molecules affects gene modulation leading to changes in behaviour such as the
release of virulence factors. Here, we use numerical methods to approximate a 2-D model of quorum sensing. It is observed
that the shape of the biofilm can have a profound effect on the onset of quorum sensing. This has serious repercussions for
experimental observations since biofilms of the same biomass but different shapes can produce quite different results. 相似文献