全文获取类型
收费全文 | 572篇 |
免费 | 43篇 |
出版年
2023年 | 12篇 |
2022年 | 1篇 |
2021年 | 18篇 |
2020年 | 7篇 |
2019年 | 10篇 |
2018年 | 9篇 |
2017年 | 14篇 |
2016年 | 23篇 |
2015年 | 27篇 |
2014年 | 27篇 |
2013年 | 46篇 |
2012年 | 52篇 |
2011年 | 37篇 |
2010年 | 21篇 |
2009年 | 17篇 |
2008年 | 37篇 |
2007年 | 18篇 |
2006年 | 23篇 |
2005年 | 22篇 |
2004年 | 19篇 |
2003年 | 26篇 |
2002年 | 18篇 |
2001年 | 12篇 |
2000年 | 11篇 |
1999年 | 9篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 6篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 10篇 |
1992年 | 2篇 |
1991年 | 6篇 |
1990年 | 10篇 |
1989年 | 7篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1985年 | 4篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 4篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1967年 | 1篇 |
1954年 | 1篇 |
1928年 | 1篇 |
排序方式: 共有615条查询结果,搜索用时 15 毫秒
61.
In this paper, we present a continuous attractor network model that we hypothesize will give some suggestion of the mechanisms
underlying several neural processes such as velocity tuning to visual stimulus, sensory discrimination, sensorimotor transformations,
motor control, motor imagery, and imitation. All of these processes share the fundamental characteristic of having to deal
with the dynamic integration of motor and sensory variables in order to achieve accurate sensory prediction and/or discrimination.
Such principles have already been described in the literature by other high-level modeling studies (Decety and Sommerville
in Trends Cogn Sci 7:527–533, 2003; Oztop et al. in Neural Netw 19(3):254–271, 2006; Wolpert et al. in Philos Trans R Soc
358:593–602, 2003). With respect to these studies, our work is more concerned with biologically plausible neural dynamics
at a population level. Indeed, we show that a relatively simple extension of the classical neural field models can endow these
networks with additional dynamic properties for updating their internal representation using external commands. Moreover,
an analysis of the interactions between our model and external inputs also shows interesting properties, which we argue are
relevant for a better understanding of the neural processes of the brain. 相似文献
62.
Awada M Soulage CO Meynier A Debard C Plaisancié P Benoit B Picard G Loizon E Chauvin MA Estienne M Peretti N Guichardant M Lagarde M Genot C Michalski MC 《Journal of lipid research》2012,53(10):2069-2080
Dietary intake of long-chain n-3 PUFA is now widely advised for public health and in medical practice. However, PUFA are highly prone to oxidation, producing potentially deleterious 4-hydroxy-2-alkenals. Even so, the impact of consuming oxidized n-3 PUFA on metabolic oxidative stress and inflammation is poorly described. We therefore studied such effects and hypothesized the involvement of the intestinal absorption of 4-hydroxy-2-hexenal (4-HHE), an oxidized n-3 PUFA end-product. In vivo, four groups of mice were fed for 8 weeks high-fat diets containing moderately oxidized or unoxidized n-3 PUFA. Other mice were orally administered 4-HHE and euthanized postprandially versus baseline mice. In vitro, human intestinal Caco-2/TC7 cells were incubated with 4-hydroxy-2-alkenals. Oxidized diets increased 4-HHE plasma levels in mice (up to 5-fold, P < 0.01) compared with unoxidized diets. Oxidized diets enhanced plasma inflammatory markers and activation of nuclear factor kappaB (NF-κB) in the small intestine along with decreasing Paneth cell number (up to -19% in the duodenum). Both in vivo and in vitro, intestinal absorption of 4-HHE was associated with formation of 4-HHE-protein adducts and increased expression of glutathione peroxidase 2 (GPx2) and glucose-regulated protein 78 (GRP78). Consumption of oxidized n-3 PUFA results in 4-HHE accumulation in blood after its intestinal absorption and triggers oxidative stress and inflammation in the upper intestine. 相似文献
63.
Violle C Enquist BJ McGill BJ Jiang L Albert CH Hulshof C Jung V Messier J 《Trends in ecology & evolution》2012,27(4):244-252
Despite being recognized as a promoter of diversity and a condition for local coexistence decades ago, the importance of intraspecific variance has been neglected over time in community ecology. Recently, there has been a new emphasis on intraspecific variability. Indeed, recent developments in trait-based community ecology have underlined the need to integrate variation at both the intraspecific as well as interspecific level. We introduce new T-statistics ('T' for trait), based on the comparison of intraspecific and interspecific variances of functional traits across organizational levels, to operationally incorporate intraspecific variability into community ecology theory. We show that a focus on the distribution of traits at local and regional scales combined with original analytical tools can provide unique insights into the primary forces structuring communities. 相似文献
64.
Billard A Laval V Fillinger S Leroux P Lachaise H Beffa R Debieu D 《Applied and environmental microbiology》2012,78(4):1063-1068
The evolution of fungicide resistance within populations of plant pathogens must be monitored to develop management strategies. Such monitoring often is based on microbiological tests, such as microtiter plate assays. Molecular monitoring methods can be considered if the mutations responsible for resistance have been identified. Allele-specific real-time PCR approaches, such as amplification refractory mutation system (ARMS) PCR and mismatch amplification mutation assay (MAMA) PCR, are, despite their moderate efficacy, among the most precise methods for refining SNP quantification. We describe here a new real-time PCR method, the allele-specific probe and primer amplification assay (ASPPAA PCR). This method makes use of mixtures of allele-specific minor groove binder (MGB) TaqMan probes and allele-specific primers for the fine quantification of SNPs from a pool of DNA extracted from a mixture of conidia. It was developed for a single-nucleotide polymorphism (SNP) that is responsible for resistance to the sterol biosynthesis inhibitor fungicide fenhexamid, resulting in the replacement of the phenylalanine residue (encoded by the TTC codon) in position 412 of the enzymatic target (3-ketoreductase) by a serine (TCC), valine (GTC), or isoleucine (ATC) residue. The levels of nonspecific amplification with the ASPPAA PCR were reduced at least four times below the level of currently available allele-specific real-time PCR approaches due to strong allele specificity in amplification cycles, including two allele selectors. This new method can be used to quantify a complex quadriallelic SNP in a DNA pool with a false discovery rate of less than 1%. 相似文献
65.
Malou N Tran TN Nappez C Signoli M Le Forestier C Castex D Drancourt M Raoult D 《PloS one》2012,7(2):e31744
Background
The cause of past plague pandemics was controversial but several research teams used PCR techniques and dental pulp as the primary material to reveal that they were caused by Yersinia pestis. However, the degradation of DNA limits the ability to detect ancient infections.Methods
We used for the first time immuno-PCR to detect Yersinia pestis antigens; it can detect protein concentrations 70 times lower than the standard ELISA. After determining the cut-off value, we tested 34 teeth that were obtained from mass graves of plague, and compared previous PCR results with ELISA and immuno-PCR results.Results
The immuno-PCR technique was the most sensitive (14 out of 34) followed by the PCR technique (10 out of 34) and ELISA (3 out of 34). The combination of these three methods identified 18 out of 34 (53%) teeth as presumably being from people with the plague.Conclusion
Immuno-PCR is specific (no false-positive samples were found) and more sensitive than the currently used method to detect antigens of ancient infections in dental pulp. The combination of three methods, ELISA, PCR and immuno-PCR, increased the capacity to identify ancient pathogens in dental pulp. 相似文献66.
Osorio-Madrazo A Eder M Rueggeberg M Pandey JK Harrington MJ Nishiyama Y Putaux JL Rochas C Burgert I 《Biomacromolecules》2012,13(3):850-856
Agarose hydrogels filled with cellulose nanowhiskers were strained in uniaxial stretching under different humidity conditions. The orientation of the cellulose whiskers was examined before and after testing with an X-ray laboratory source and monitored in situ during loading by synchrotron X-ray diffraction. The aim of this approach was to determine the process parameters for reorienting the cellulose nanowhiskers toward a preferential direction. Results show that a controlled drying of the hydrogel is essential to establish interactions between the matrix and the cellulose nanowhiskers which allow for a stress transfer during stretching and thereby promote their alignment. Rewetting of the sample after reorientation of the cellulose nanowhiskers circumvents a critical increase of stress. This improves the extensibility of the hydrogel and is accompanied by a further moderate alignment of the cellulose nanowhiskers. Following this protocol, cellulose nanowhiskers with an initial random distribution can be reoriented toward a preferential direction, creating anisotropic nanocomposites. 相似文献
67.
Whitehead TA Chevalier A Song Y Dreyfus C Fleishman SJ De Mattos C Myers CA Kamisetty H Blair P Wilson IA Baker D 《Nature biotechnology》2012,30(6):543-548
We show that comprehensive sequence-function maps obtained by deep sequencing can be used to reprogram interaction specificity and to leapfrog over bottlenecks in affinity maturation by combining many individually small contributions not detectable in conventional approaches. We use this approach to optimize two computationally designed inhibitors against H1N1 influenza hemagglutinin and, in both cases, obtain variants with subnanomolar binding affinity. The most potent of these, a 51-residue protein, is broadly cross-reactive against all influenza group 1 hemagglutinins, including human H2, and neutralizes H1N1 viruses with a potency that rivals that of several human monoclonal antibodies, demonstrating that computational design followed by comprehensive energy landscape mapping can generate proteins with potential therapeutic utility. 相似文献
68.
Background
Visual behavior is known to be atypical in Autism Spectrum Disorders (ASD). Monitor-based eye-tracking studies have measured several of these atypicalities in individuals with Autism. While atypical behaviors are known to be accentuated during natural interactions, few studies have been made on gaze behavior in natural interactions. In this study we focused on i) whether the findings done in laboratory settings are also visible in a naturalistic interaction; ii) whether new atypical elements appear when studying visual behavior across the whole field of view.Methodology/Principal Findings
Ten children with ASD and ten typically developing children participated in a dyadic interaction with an experimenter administering items from the Early Social Communication Scale (ESCS). The children wore a novel head-mounted eye-tracker, measuring gaze direction and presence of faces across the child''s field of view. The analysis of gaze episodes to faces revealed that children with ASD looked significantly less and for shorter lapses of time at the experimenter. The analysis of gaze patterns across the child''s field of view revealed that children with ASD looked downwards and made more extensive use of their lateral field of view when exploring the environment.Conclusions/Significance
The data gathered in naturalistic settings confirm findings previously obtained only in monitor-based studies. Moreover, the study allowed to observe a generalized strategy of lateral gaze in children with ASD when they were looking at the objects in their environment. 相似文献69.
Billard C 《Molecular cancer research : MCR》2012,10(6):673-676
Despite real advances made in chemoimmunotherapy, chronic lymphocytic leukemia (CLL) is still an incurable disease. New therapeutic strategies based on the restoration of the cell death program seemed relevant. Some members of the Bcl-2 family are critical players in the defective apoptotic program in CLL cells and/or targets of apoptosis inducers in vitro. The concept of BH3 mimetics has led to the characterization of small molecules mimicking proapoptotic BH3-only members of the Bcl-2 family by their ability to bind and antagonize the prosurvival members. Some putative or actual BH3 mimetics are already being tested in clinical trials with somewhat promising results. However, none of them has a high enough interaction affinity with Mcl-1, a crucial antiapoptotic factor in CLL. It has been suggested that resistance to BH3 mimetics can be overcome by using inhibitors of Mcl-1 expression. An alternative and more direct strategy is to design mimetics of the Noxa BH3 domain, which is a specific antagonistic Mcl-1 ligand. The development of such Noxa-like BH3 mimetics, capable of directly interacting with Mcl-1 and efficiently neutralizing its antiapoptotic activity, is extremely important to evaluate their impact on the clinical outcome of patients with CLL. 相似文献
70.
Pupylation is a post-translational protein modification occurring in actinobacteria through which the small, intrinsically disordered protein Pup (prokaryotic ubiquitin-like protein) is conjugated to lysine residues of proteins, marking them for proteasomal degradation. Although functionally related to ubiquitination, pupylation is carried out by different enzymes that are evolutionarily linked to bacterial carboxylate-amine ligases. Here, we compare the mechanism of Pup-conjugation to target proteins with ubiquitination, describe the evolutionary emergence of pupylation and discuss the importance of this pathway for survival of Mycobacterium tuberculosis in the host. 相似文献