全文获取类型
收费全文 | 4104篇 |
免费 | 306篇 |
国内免费 | 2篇 |
专业分类
4412篇 |
出版年
2023年 | 12篇 |
2022年 | 35篇 |
2021年 | 58篇 |
2020年 | 47篇 |
2019年 | 51篇 |
2018年 | 53篇 |
2017年 | 73篇 |
2016年 | 92篇 |
2015年 | 187篇 |
2014年 | 184篇 |
2013年 | 258篇 |
2012年 | 331篇 |
2011年 | 352篇 |
2010年 | 225篇 |
2009年 | 203篇 |
2008年 | 297篇 |
2007年 | 242篇 |
2006年 | 251篇 |
2005年 | 232篇 |
2004年 | 225篇 |
2003年 | 237篇 |
2002年 | 204篇 |
2001年 | 48篇 |
2000年 | 34篇 |
1999年 | 52篇 |
1998年 | 52篇 |
1997年 | 36篇 |
1996年 | 45篇 |
1995年 | 41篇 |
1994年 | 31篇 |
1993年 | 20篇 |
1992年 | 36篇 |
1991年 | 13篇 |
1990年 | 20篇 |
1989年 | 16篇 |
1988年 | 15篇 |
1987年 | 13篇 |
1986年 | 7篇 |
1985年 | 14篇 |
1984年 | 13篇 |
1983年 | 13篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1977年 | 7篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1971年 | 3篇 |
1915年 | 1篇 |
排序方式: 共有4412条查询结果,搜索用时 15 毫秒
81.
82.
Omar Soukarieh Pascaline Gaildrat Mohamad Hamieh Aurélie Drouet Stéphanie Baert-Desurmont Thierry Frébourg Mario Tosi Alexandra Martins 《PLoS genetics》2016,12(1)
The identification of a causal mutation is essential for molecular diagnosis and clinical management of many genetic disorders. However, even if next-generation exome sequencing has greatly improved the detection of nucleotide changes, the biological interpretation of most exonic variants remains challenging. Moreover, particular attention is typically given to protein-coding changes often neglecting the potential impact of exonic variants on RNA splicing. Here, we used the exon 10 of MLH1, a gene implicated in hereditary cancer, as a model system to assess the prevalence of RNA splicing mutations among all single-nucleotide variants identified in a given exon. We performed comprehensive minigene assays and analyzed patient’s RNA when available. Our study revealed a staggering number of splicing mutations in MLH1 exon 10 (77% of the 22 analyzed variants), including mutations directly affecting splice sites and, particularly, mutations altering potential splicing regulatory elements (ESRs). We then used this thoroughly characterized dataset, together with experimental data derived from previous studies on BRCA1, BRCA2, CFTR and NF1, to evaluate the predictive power of 3 in silico approaches recently described as promising tools for pinpointing ESR-mutations. Our results indicate that ΔtESRseq and ΔHZEI-based approaches not only discriminate which variants affect splicing, but also predict the direction and severity of the induced splicing defects. In contrast, the ΔΨ-based approach did not show a compelling predictive power. Our data indicates that exonic splicing mutations are more prevalent than currently appreciated and that they can now be predicted by using bioinformatics methods. These findings have implications for all genetically-caused diseases. 相似文献
83.
84.
Sébastien Breurec Noémie Vanel Petulla Bata Lo?c Chartier Alain Farra Lo?c Favennec Thierry Franck Tamara Giles-Vernick Jean-Chrysostome Gody Liem Binh Luong Nguyen Manuella Onambélé Clotaire Rafa? Romy Razakandrainibe Laura Tondeur Vianney Tricou Philippe Sansonetti Muriel Vray 《PLoS neglected tropical diseases》2016,10(1)
Background
In Sub-Saharan Africa, infectious diarrhea is a major cause of morbidity and mortality. A case-control study was conducted to identify the etiology of diarrhea and to describe its main epidemiologic risk factors among hospitalized children under five years old in Bangui, Central African Republic.Methods
All consecutive children under five years old hospitalized for diarrhea in the Pediatric Complex of Bangui for whom a parent’s written consent was provided were included. Controls matched by age, sex and neighborhood of residence of each case were included. For both cases and controls, demographic, socio-economic and anthropometric data were recorded. Stool samples were collected to identify enteropathogens at enrollment. Clinical examination data and blood samples were collected only for cases.Results
A total of 333 cases and 333 controls was recruited between December 2011 and November 2013. The mean age of cases was 12.9 months, and 56% were male. The mean delay between the onset of first symptoms and hospital admission was 3.7 days. Blood was detected in 5% of stool samples from cases. Cases were significantly more severely or moderately malnourished than controls. One of the sought-for pathogens was identified in 78% and 40% of cases and controls, respectively. Most attributable cases of hospitalized diarrhea were due to rotavirus, with an attributable fraction of 39%. Four other pathogens were associated with hospitalized diarrhea: Shigella/EIEC, Cryptosporidium parvum/hominis, astrovirus and norovirus with attributable fraction of 9%, 10%, 7% and 7% respectively. Giardia intestinalis was found in more controls than cases, with a protective fraction of 6%.Conclusions
Rotavirus, norovirus, astrovirus, Shigella/EIEC, Cryptosporidium parvum/hominis were found to be positively associated with severe diarrhea: while Giardia intestinalis was found negatively associated. Most attributable episodes of severe diarrhea were associated with rotavirus, highlighting the urgent need to introduce the rotavirus vaccine within the CAR’s Expanded Program on Immunization. The development of new medicines, vaccines and rapid diagnostic tests that can be conducted at the bedside should be high priority for low-resource countries. 相似文献85.
Lophelia pertusa is the dominant reef-building organism of cold-water coral reefs, and is known to produce significant amounts of mucus, which could involve an important metabolic cost. Mucus is involved in particle removal and feeding processes, yet the triggers and dynamics of mucus production are currently still poorly described because the existing tools to study these processes are not appropriate. Using a novel microscopic technique—digital holographic microscopy (DHM)–we studied the mucus release of L. pertusa under various experimental conditions. DHM technology permits μm-scale observations and allows the visualization of transparent mucoid substances in real time without staining. Fragments of L. pertusa were first maintained in flow-through chambers without stressors and imaged with DHM, then exposed to various stressors (suspended particles, particulate food and air exposure) and re-imaged. Under non-stressed conditions no release of mucus was observed, whilst mucus strings and sheaths were produced in response to suspended particles (activated charcoal and drill cuttings sediment) i.e. in a stressed condition. Mucus strings and so-called ‘string balls’ were also observed in response to exposure to particulate food (brine shrimp Artemia salina). Upon air-exposure, mucus production was clearly visible once the fragments were returned to the flow chamber. Distinct optical properties such as optical path length difference (OPD) were measured with DHM in response to the various stimuli suggesting that different mucus types are produced by L. pertusa. Mucus produced to reject particles is similar in refractive index to the surrounding seawater, suggesting that the energy content of this mucus is low. In contrast, mucus produced in response to either food particle addition or air exposure had a higher refractive index, suggesting a higher metabolic investment in the production of these mucoid substances. This paper shows for the first time the potential of DHM technology for the detection, characterization and quantification of mucus production through OPD measurements in L. pertusa. 相似文献
86.
87.
Evidence for different,host‐dependent functioning of Rx against both wild‐type and recombinant Pepino mosaic virus 下载免费PDF全文
Celia R. A. Duff‐Farrier Thierry Candresse Andy M. Bailey Neil Boonham Gary D. Foster 《Molecular Plant Pathology》2016,17(1):120-126
The potato Rx gene provides resistance against Pepino mosaic virus (PepMV) in tomato; however, recent work has suggested that the resistance conferred may not be durable. Resistance breaking can probably be attributed to multiple mutations observed to accumulate in the capsid protein (CP) region of resistance‐breaking isolates, but this has not been confirmed through directed manipulation of an infectious PepMV clone. The present work describes the introduction of two specific mutations, A‐T78 and A‐T114, into the coat protein minimal elicitor region of an Rx‐controlled PepMV isolate of the EU genotype. Enzyme‐linked immunosorbent assay (ELISA) and phenotypic evaluation were conducted in three Rx‐expressing and wild‐type solanaceous hosts: Nicotiana benthamiana, Nicotiana tabacum and Solanum lycopersicum. Mutation A‐T78 alone was sufficient to confer Rx‐breaking activity in N. benthamiana and S. lycopersicum, whereas mutation A‐T114 was found to be associated, in most cases, with a secondary A‐D100 mutation to break Rx‐mediated resistance in S. lycopersicum. These results suggest that the need for a second, fitness‐restoring mutation may be dependent on the PepMV mutant under consideration. Both mutations conferred Rx breaking in S. lycopersicum, whereas neither conferred Rx breaking in N. tabacum and only A‐T78 allowed Rx breaking in N. benthamiana, suggesting that Rx may function in a different manner depending on the genetic background in which it is present. 相似文献
88.
Bihag Anothumakkool Simon Wiemers‐Meyer Dominique Guyomard Martin Winter Thierry Brousse Joel Gaubicher 《Liver Transplantation》2019,9(27)
An industry‐relevant method for pre‐lithiation of lithium‐ion capacitors to balance the first charge irreversibility is demonstrated, which addresses the prime bottleneck for their market integration. Based on a composite positive electrode that integrates pyrene monomers and an insoluble lithiated base, Li3PO4, a “cascade‐type” process involving two consecutive irreversible reactions is proposed: i) oxidative electropolymerization of the pyrene moieties releases electrons and protons; ii) protons are captured by Li3PO4 and exchanged for a stoichiometric amount of Li+ into the electrolyte. (1H, 19F, and 31P) NMR spectroscopy, operando X‐ray diffraction, and Raman spectroscopy support this mechanism. By decoupling the irreversible source of lithium ions from electrons, the cascade‐type pre‐lithiation allows the simultaneous enhancement of the capacity of the positive electrode, thanks to p‐doping of the resulting polymer. Remarkably, the proton scavenging properties of Li3PO4 also boost the polymerization process, which enables a 16% increase in capacity without detrimental effect on power properties and cyclability. Full cells integrating a cheap carbon black based negative electrode, show much‐improved capacity of 17 mAh g‐1electrodes (44 F g‐1electrodes, 3–4.4 V) and excellent stability over 2200 cycles at 1 A g‐1. Thanks to its versatile chemistry and flexibility this approach in principle can be applied to any kind of ion‐battery. 相似文献
89.
Alexis De Wever Karim Benzerara Margot Coutaud Graldine Caumes Mlanie Poinsot Friel Skouri‐Panet Thierry Laurent Elodie Duprat Muriel Gugger 《Geobiology》2019,17(6):676-690
Several species of cyanobacteria biomineralizing intracellular amorphous calcium carbonates (ACC) were recently discovered. However, the mechanisms involved in this biomineralization process and the determinants discriminating species forming intracellular ACC from those not forming intracellular ACC remain unknown. Recently, it was hypothesized that the intensity of Ca uptake (i.e., how much Ca was scavenged from the extracellular solution) might be a major parameter controlling the capability of a cyanobacterium to form intracellular ACC. Here, we tested this hypothesis by systematically measuring the Ca uptake by a set of 52 cyanobacterial strains cultured in the same growth medium. The results evidenced a dichotomy among cyanobacteria regarding Ca sequestration capabilities, with all strains forming intracellular ACC incorporating significantly more calcium than strains not forming ACC. Moreover, Ca provided at a concentration of 50 μM in BG‐11 was shown to be limiting for the growth of some of the strains forming intracellular ACC, suggesting an overlooked quantitative role of Ca for these strains. All cyanobacteria forming intracellular ACC contained at least one gene coding for a mechanosensitive channel, which might be involved in Ca influx, as well as at least one gene coding for a Ca2+/H+ exchanger and membrane proteins of the UPF0016 family, which might be involved in active Ca transport either from the cytosol to the extracellular solution or the cytosol toward an intracellular compartment. Overall, massive Ca sequestration may have an indirect role by allowing the formation of intracellular ACC. The latter may be beneficial to the growth of the cells as a storage of inorganic C and/or a buffer of intracellular pH. Moreover, high Ca scavenging by cyanobacteria biomineralizing intracellular ACC, a trait shared with endolithic cyanobacteria, suggests that these cyanobacteria should be considered as potentially significant geochemical reservoirs of Ca. 相似文献
90.
Armelle M. Braud Pierre Gaudin Alice Hazotte Cécile Le Guern Thierry Lebeau 《International journal of phytoremediation》2019,21(11):1072-1079
AbstractThe development of more sustainable remediation techniques has been receiving greater attention, as an alternative to soil excavation plan in urban gardens. An in situ phytoextraction experiment with buckwheat (Fagopyrum esculentum) was performed with a 5?mmol kg?1 citric acid (CA) application. Joint experiments under laboratory conditions were conducted using various cultivars of F. esculentum in two soils with a Pb contamination of either geogenic or anthropogenic origin and various chelate concentrations. Results show that a minimum dose of 50?mmol kg?1 of CA is required to lower soil pH and raise the concentration of mobile Pb–CaCl2 for both soils. Consequently, Pb shoot uptake is increased from 6.3 to 8.9 times depending on soil type. Phytoextraction efficiency is found to be 1.3 to 2.0 times higher in the anthropogenic contaminated soil than in the soil with geogenic Pb. A scale effect has also been identified since Pb root accumulation under laboratory conditions was 2.4 times higher than in the field experiment. Despite an increase in the Pb extraction rate with CA, buckwheat appears to lack the efficiency needed to remove Pb in moderately contaminated soils. The calculated remediation period would last 166?years to remove the mobile Pb fraction. 相似文献