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71.
Among songbirds, the capacity to associate particular songs with particular singers (i.e., vocal recognition) forms the cognitive basis for more complex communication behaviors such as female choice and territoriality. In the present study, we combine operant conditioning techniques and excitotoxic lesions to the forebrain nucleus HVc to examine the role of this region in the discrimination, associative learning, and categorization of conspecific song. We trained adult male and female European starlings, Sturnus vulgaris, to recognize simultaneously the songs of several conspecific males. Then, using a series of transfer procedures, we demonstrate that correct recognition does not generalize to song bouts containing novel motifs from familiar singers. This suggests that starlings do not make use of individually invariant source or filter characteristics for vocal recognition. We then lesioned a portion of HVc bilaterally with ibotenic acid, and exposed the birds to a series of manipulations testing the discrimination, associative learning, and categorization of conspecific song. The lesions attenuated song production among males, but retention of the basic recognition task (i.e., maintenance of the discrimination) was unaffected. However, when the response contingencies were reversed-as a test of associative learning independent of discrimination-the initial performance and subsequent learning rate were negatively correlated with the size of the HVc lesions. This suggests that HVc plays a role in the formation of associations between a song and some referent. The results of this study are discussed in light of earlier claims regarding the role of HVc in the perceptual processing of conspecific song. 相似文献
72.
Evolutionary distances for protein-coding sequences: modeling site- specific residue frequencies 总被引:13,自引:8,他引:5
Estimation of evolutionary distances from coding sequences must take into
account protein-level selection to avoid relative underestimation of longer
evolutionary distances. Current modeling of selection via site-to-site rate
heterogeneity generally neglects another aspect of selection, namely
position-specific amino acid frequencies. These frequencies determine the
maximum dissimilarity expected for highly diverged but functionally and
structurally conserved sequences, and hence are crucial for estimating long
distances. We introduce a codon- level model of coding sequence evolution
in which position-specific amino acid frequencies are free parameters. In
our implementation, these are estimated from an alignment using methods
described previously. We use simulations to demonstrate the importance and
feasibility of modeling such behavior; our model produces linear distance
estimates over a wide range of distances, while several alternative models
underestimate long distances relative to short distances. Site-to-site
differences in rates, as well as synonymous/nonsynonymous and
first/second/third-codon-position differences, arise as a natural
consequence of the site-to-site differences in amino acid frequencies.
相似文献
73.
74.
Nicholas J. Croucher Lisa Kagedan Claudette M. Thompson Julian Parkhill Stephen D. Bentley Jonathan A. Finkelstein Marc Lipsitch William P. Hanage 《PLoS genetics》2015,11(3)
Streptococcus pneumoniae isolates typically express one of over 90 immunologically distinguishable polysaccharide capsules (serotypes), which can be classified into “serogroups” based on cross-reactivity with certain antibodies. Pneumococci can alter their serotype through recombinations affecting the capsule polysaccharide synthesis (cps) locus. Twenty such “serotype switching” events were fully characterised using a collection of 616 whole genome sequences from systematic surveys of pneumococcal carriage. Eleven of these were within-serogroup switches, representing a highly significant (p < 0.0001) enrichment based on the observed serotype distribution. Whereas the recombinations resulting in between-serogroup switches all spanned the entire cps locus, some of those that caused within-serogroup switches did not. However, higher rates of within-serogroup switching could not be fully explained by either more frequent, shorter recombinations, nor by genetic linkage to genes involved in β–lactam resistance. This suggested the observed pattern was a consequence of selection for preserving serogroup. Phenotyping of strains constructed to express different serotypes in common genetic backgrounds was used to test whether genotypes were physiologically adapted to particular serogroups. These data were consistent with epistatic interactions between the cps locus and the rest of the genome that were specific to serotype, but not serogroup, meaning they were unlikely to account for the observed distribution of capsule types. Exclusion of these genetic and physiological hypotheses suggested future work should focus on alternative mechanisms, such as host immunity spanning multiple serotypes within the same serogroup, which might explain the observed pattern. 相似文献
75.
Masaya Ito Kate H. Bentley Yuki Oe Shun Nakajima Hiroko Fujisato Noriko Kato Mitsuhiro Miyamae Ayako Kanie Masaru Horikoshi David H. Barlow 《PloS one》2015,10(4)
Background
The Overall Depression Severity and Impairment Scale (ODSIS) is a brief, five-item measure for assessing the frequency and intensity of depressive symptoms, as well as functional impairments in pleasurable activities, work or school, and interpersonal relationships due to depression. Although this scale is expected to be useful in various psychiatric and mental health settings, the reliability, validity, and interpretability have not yet been fully examined. This study was designed to examine the reliability, factorial, convergent, and discriminant validity of a Japanese version of the ODSIS, as well as its ability to distinguish between individuals with and without a major depressive disorder diagnosis.Methods
From a pool of registrants at an internet survey company, 2830 non-clinical and clinical participants were selected randomly (619 with major depressive disorder, 619 with panic disorder, 576 with social anxiety disorder, 645 with obsessive–compulsive disorder, and 371 non-clinical panelists). Participants were asked to respond to the ODSIS and conventional measures of depression, functional impairment, anxiety, neuroticism, satisfaction with life, and emotion regulation.Results
Exploratory and confirmatory factor analysis of three split subsamples indicated the unidimensional factor structure of ODSIS. Multi-group confirmatory factor analysis showed invariance of factor loadings between non-clinical and clinical subsamples. The ODSIS also showed excellent internal consistency and test–retest intraclass correlation coefficients. Convergence and discriminance of the ODSIS with various measures were in line with our expectations. Receiver operating characteristic curve analyses showed that the ODSIS was able to detect a major depressive syndrome accurately.Conclusions
This study supports the reliability and validity of ODSIS in a non-western population, which can be interpreted as demonstrating cross-cultural validity. 相似文献76.
Nandhakumar Thayanidhi Jared R. Helm Deborah C. Nycz Marvin Bentley Yingjian Liang Jesse C. Hay 《Molecular biology of the cell》2010,21(11):1850-1863
Toxicity of human α-synuclein when expressed in simple organisms can be suppressed by overexpression of endoplasmic reticulum (ER)-to-Golgi transport machinery, suggesting that inhibition of constitutive secretion represents a fundamental cause of the toxicity. Whether similar inhibition in mammals represents a cause of familial Parkinson''s disease has not been established. We tested elements of this hypothesis by expressing human α-synuclein in mammalian kidney and neuroendocrine cells and assessing ER-to-Golgi transport. Overexpression of wild type or the familial disease-associated A53T mutant α-synuclein delayed transport by up to 50%; however, A53T inhibited more potently. The secretory delay occurred at low expression levels and was not accompanied by insoluble α-synuclein aggregates or mistargeting of transport machinery, suggesting a direct action of soluble α-synuclein on trafficking proteins. Co-overexpression of ER/Golgi arginine soluble N-ethylmaleimide-sensitive factor attachment protein receptors (R-SNAREs) specifically rescued transport, indicating that α-synuclein antagonizes SNARE function. Ykt6 reversed α-synuclein inhibition much more effectively than sec22b, suggesting a possible neuroprotective role for the enigmatic high expression of ykt6 in neurons. In in vitro reconstitutions, purified α-synuclein A53T protein specifically inhibited COPII vesicle docking and fusion at a pre-Golgi step. Finally, soluble α-synuclein A53T directly bound ER/Golgi SNAREs and inhibited SNARE complex assembly, providing a potential mechanism for toxic effects in the early secretory pathway. 相似文献
77.
Mao H Graziano JJ Chase TM Bentley CA Bazirgan OA Reddy NP Song BD Smider VV 《Nature biotechnology》2010,28(11):1195-1202
Antibody discovery typically uses hybridoma- or display-based selection approaches, which lack the advantages of directly screening spatially addressed compound libraries as in small-molecule discovery. Here we apply the latter strategy to antibody discovery, using a library of ~10,000 human germline antibody Fabs created by de novo DNA synthesis and automated protein expression and purification. In multiplexed screening assays, we obtained specific hits against seven of nine antigens. Using sequence-activity relationships and iterative mutagenesis, we optimized the binding affinities of two hits to the low nanomolar range. The matured Fabs showed full and partial antagonism activities in cell-based assays. Thus, protein drug leads can be discovered using surprisingly small libraries of proteins with known sequences, questioning the requirement for billions of members in an antibody discovery library. This methodology also provides sequence, expression and specificity information at the first step of the discovery process, and could enable novel antibody discovery in functional screens. 相似文献
78.
Zhenrong Xu Salvacion Cacatian Jing Yuan Robert D. Simpson Lanqi Jia Wei Zhao Colin M. Tice Patrick T. Flaherty Joan Guo Alexey Ishchenko Suresh B. Singh Zhongren Wu Brian M. McKeever Boyd B. Scott Yuri Bukhtiyarov Jennifer Berbaum Jennifer Mason Reshma Panemangalore Maria Grazia Cappiello Ross Bentley David A. Claremon 《Bioorganic & medicinal chemistry letters》2010,20(2):694-699
Structure-guided drug design led to new alkylamine renin inhibitors with improved in vitro and in vivo potency. Lead compound 21a, has an IC50 of 0.83 nM for the inhibition of human renin in plasma (PRA). Oral administration of 21a at 10 mg/kg resulted in >20 h reduction of blood pressure in a double transgenic rat model of hypertension. 相似文献
79.
Jessica AB van Nies Rute B Marques Stella Trompet Zuzana de Jong Fina AS Kurreeman Rene EM Toes J Wouter Jukema Tom WJ Huizinga Annette HM van der Helm-van Mil 《Arthritis research & therapy》2010,12(2):R38
Introduction
Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients. 相似文献80.
Melek Güler-Yüksel Naomi B Klarenbeek Yvonne PM Goekoop-Ruiterman Jeska K de Vries-Bouwstra Sjoerd M van der Kooij Andreas H Gerards H Karel Ronday Tom WJ Huizinga Ben AC Dijkmans Cornelia F Allaart Willem F Lems 《Arthritis research & therapy》2010,12(3):R96