全文获取类型
收费全文 | 1660篇 |
免费 | 151篇 |
专业分类
1811篇 |
出版年
2023年 | 14篇 |
2022年 | 34篇 |
2021年 | 61篇 |
2020年 | 36篇 |
2019年 | 48篇 |
2018年 | 49篇 |
2017年 | 48篇 |
2016年 | 70篇 |
2015年 | 105篇 |
2014年 | 95篇 |
2013年 | 109篇 |
2012年 | 128篇 |
2011年 | 135篇 |
2010年 | 67篇 |
2009年 | 65篇 |
2008年 | 84篇 |
2007年 | 85篇 |
2006年 | 59篇 |
2005年 | 57篇 |
2004年 | 48篇 |
2003年 | 47篇 |
2002年 | 34篇 |
2001年 | 31篇 |
2000年 | 31篇 |
1999年 | 29篇 |
1998年 | 13篇 |
1997年 | 14篇 |
1996年 | 11篇 |
1995年 | 12篇 |
1994年 | 15篇 |
1992年 | 13篇 |
1991年 | 11篇 |
1990年 | 14篇 |
1989年 | 10篇 |
1988年 | 7篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 13篇 |
1984年 | 12篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 10篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1975年 | 7篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1968年 | 4篇 |
排序方式: 共有1811条查询结果,搜索用时 0 毫秒
991.
We use first principles of population genetics to model the evolution of proteins under persistent positive selection (PPS). PPS may occur when organisms are subjected to persistent environmental change, during adaptive radiations, or in host–pathogen interactions. Our mutation–selection model indicates protein evolution under PPS is an irreversible Markov process, and thus proteins under PPS show a strongly asymmetrical distribution of selection coefficients among amino acid substitutions. Our model shows the criteria (where ω is the ratio of nonsynonymous over synonymous codon substitution rates) to detect positive selection is conservative and indeed arbitrary, because in real proteins many mutations are highly deleterious and are removed by selection even at positively selected sites. We use a penalized-likelihood implementation of the PPS model to successfully detect PPS in plant RuBisCO and influenza HA proteins. By directly estimating selection coefficients at protein sites, our inference procedure bypasses the need for using ω as a surrogate measure of selection and improves our ability to detect molecular adaptation in proteins. 相似文献
992.
Marcelo Cunha Federico Costa Guilherme S. Ribeiro Marilia S. Carvalho Renato B. Reis Nivison Nery Jr Lauren Pischel Edilane L. Gouveia Andreia C. Santos Adriano Queiroz Elsio A. Wunder Jr. Mitermayer G. Reis Peter J Diggle Albert I. Ko 《PLoS neglected tropical diseases》2022,16(4)
BackgroundLeptospirosis is an important public health problem affecting vulnerable urban slum populations in developing country settings. However, the complex interaction of meteorological factors driving the temporal trends of leptospirosis remain incompletely understood.Methods and findingsFrom March 1996—March 2010, we investigated the association between the weekly incidence of leptospirosis and meteorological anomalies in the city of Salvador, Brazil by using a dynamic generalized linear model that accounted for time lags, overall trend, and seasonal variation. Our model showed an increase of leptospirosis cases associated with higher than expected rainfall, lower than expected temperature and higher than expected humidity. There was a lag of one-to-two weeks between weekly values for significant meteorological variables and leptospirosis incidence. Independent of the season, a weekly cumulative rainfall anomaly of 20 mm increased the risk of leptospirosis by 12% compared to a week following the expected seasonal pattern. Finally, over the 14-year study period, the annual incidence of leptospirosis decreased significantly by a factor of 2.7 (8.3 versus 3.0 per 100,000 people), independently of variations in climate.ConclusionsStrategies to control leptospirosis should focus on avoiding contact with contaminated sources of Leptospira as well as on increasing awareness in the population and health professionals within the short time window after low-level or extreme high-level rainfall events. Increased leptospirosis incidence was restricted to one-to-two weeks after those events suggesting that infectious Leptospira survival may be limited to short time intervals. 相似文献
993.
Somatostatin and CCK-8 modulate release of striatal amino acids: role of dopamine receptors 总被引:1,自引:0,他引:1
The effects of somatostatin (SOM) and cholecystokinin octapeptide (CCK-8) on basal and potassium-evoked release of neurotransmitter amino acids were investigated in slices of rat caudate nucleus (CN) and, for comparison, cerebral cortex (CX). Endogenous aspartate (Asp), glutamate (Glu), glycine (Gly), and gamma-aminobutyric acid (GABA) were measured by high performance liquid chromatography. In both CN and CX, potassium (5-55 mM) produced a concentration-dependent increase in the release of Asp, Glu, Gly, and GABA in the presence of extracellular Ca2+. CCK-8 (1 microM) stimulated in CN the basal and K+-evoked release of Gly to 231% and 160% of control, respectively; this effect was blocked by sulpiride (SULP), a dopamine receptor antagonist. In contrast, SOM (1 microM) inhibited the K+-evoked release of Glu in CN by 26%, an effect that was not blocked by SULP. SOM and CCK-8 did not significantly affect the basal or K+ (35 mM)-evoked release of other amino acids in the CN or of any amino acids in CX. The results indicate that: CCK-8 facilitation of Gly release is dependent of Gly release is dependent on dopamine receptor activation, whereas the inhibition by SOM of Glu release is not: and the effects of SOM and CCK-8 are specific with respect to the brain region affected. 相似文献
994.
Matheus Filgueira Bezerra Camila Cavalcanti Xavier Alzira Maria Paiva de Almeida Christian Robson de Souza Reis 《PLoS neglected tropical diseases》2022,16(5)
BackgroundThe Hemagglutination assay (HA) is widely used in plague diagnosis, however, it has a subjective interpretation and demands high amounts of antigen and other immunobiological supplies. On the other hand, the conventional Anti-IgG ELISA is limited by the need of specific conjugates for multiple plague hosts, which leaves a gap for new diagnostic methods able to cover both the diagnosis of human cases and the epidemiological surveillance of multiple sentinel species.MethodsWe developed an ELISA Protein A-peroxidase method to detect anti-F1 antibodies across several species, including humans. To determine the cut-off and performance rates, HA results from 288 samples (81 rabbits, 64 humans, 66 rodents and 77 dogs) were used as reference. Next, we evaluated the agreement between Protein A-ELISA and Anti-IgG ELISA in an expanded sample set (n = 487).ResultsOptimal conditions were found with 250ng/well of F1 and 1:500 serum dilution. Protein A-ELISA showed high repeatability and reproducibility. We observed good correlation rates between the Protein A and IgG ELISAs optical densities and a higher positive/negative OD ratio for the Protein A-ELISA method. The overall sensitivity, specificity and area under the curve for Protein A-ELISA were 94%, 99% and 0.99, respectively. Similar results were observed for each species separately. In the analysis of the expanded sample set, there was a strong agreement between Protein A and IgG assays (kappa = 0.97). Furthermore, there was no cross-reaction with other common infectious diseases, such as dengue, Zika, Chagas disease, tuberculosis (humans) and ehrlichiosis, anaplasmosis and leishmaniasis (dogs).ConclusionsAltogether, the Protein A-ELISA showed high performance when compared both to HA and Anti-IgG ELISA, with a polyvalent single protocol that requires reduced amounts of antigen and can be employed to any plague hosts. 相似文献
995.
Sofia Ribeiro Eugenia Pugliese Stefanie H. Korntner Emanuel M. Fernandes Manuela E. Gomes Rui L. Reis Alan O'Riordan Yves Bayon Dimitrios I. Zeugolis 《Engineering in Life Science》2022,22(10):619
The combined effect of surface topography and substrate rigidity in stem cell cultures is still under‐investigated, especially when biodegradable polymers are used. Herein, we assessed human bone marrow stem cell response on aliphatic polyester substrates as a function of anisotropic grooved topography and rigidity (7 and 12 kPa). Planar tissue culture plastic (TCP, 3 GPa) and aliphatic polyester substrates were used as controls. Cell morphology analysis revealed that grooved substrates caused nuclei orientation/alignment in the direction of the grooves. After 21 days in osteogenic and chondrogenic media, the 3 GPa TCP and the grooved 12 kPa substrate induced significantly higher calcium deposition and alkaline phosphatase (ALP) activity and glycosaminoglycan (GAG) deposition, respectively, than the other groups. After 14 days in tenogenic media, the 3 GPa TCP upregulated four and downregulated four genes; the planar 7 kPa substrate upregulated seven genes and downregulated one gene; and the grooved 12 kPa substrate upregulated seven genes and downregulated one gene. After 21 days in adipogenic media, the softest (7 kPa) substrates induced significantly higher oil droplet deposition than the other substrates and the grooved substrate induced significantly higher droplet deposition than the planar. Our data pave the way for more rational design of bioinspired constructs. 相似文献
996.
997.
Julio Cesar da Costa Paulo Henrique Borges Luiz Fernando Ramos-Silva Vinicius Muller Reis Weber Alexandre Moreira Enio Ricardo Vaz Ronque 《Biology of sport / Institute of Sport》2023,40(1):51
The objective of this study was to investigate the relative contributions of body size, skeletal age, and motor performance variables with technical actions through an ecological model during small-sided soccer games, and the interaction of biological maturation with technical and motor performance in young players. In this cross-sectional study, eighty-two young players (14.4 ± 1.1 years), belonging to state-level soccer teams and divided by category (U-13 and U-15), were included. Players having an injury in the evaluation period were not included in the study. Measurements of body size, skeletal age (SA), motor tests, and technical actions in small-sided games (SSG) were performed (3 × 3 plus goalkeeper) in two periods (halves) of four minutes. Differences between age groups were found for SA (ES = -2.36), chronological age (ES = -3.89), body mass (ES = -2.09), height (ES = -1.90), and fat-free mass (ES = -2.09). Positive associations were found between body size (R = 0.43 to R = 0.48) and manipulation (R = 0.50 to R = 0.52) indicators and numbers of technical actions (CB and SS), except for stature with LB (R = -0.42) in the U-13 age group. In the U-15 category, skeletal age (R = -0.29 to R = -0.30) and body mass (R = -0.28 to R = -0.29) were negatively associated with the number of technical actions (RB, NB, LB, and OB) (P > 0.05) and positively with the balance with LB (R = 0.26). In conclusion, body size, SA, and motor performance influenced technical actions in SSG differentially in each category. U-13 heavier players and those with a better motor performance presented higher involvement due to the higher 相似文献
998.
Diaphragmatic Spinal Muscular Atrophy with Respiratory Distress Is Heterogeneous, and One Form Is Linked to Chromosome 11q13-q21 总被引:3,自引:0,他引:3 下载免费PDF全文
999.
S H Andri?o-Escarso A M Soares V M Rodrigues A C Mancin M L Reis G Ballejo J R Giglio 《Biochemistry and molecular biology international》1999,47(4):699-706
The isolation and partial characterization of a serine protease with arginine ester hydrolase activity from Bothrops jararacussu snake venom are described. The purification procedure consisted of a gel filtration of the crude venom on Sephadex G-75 followed by an ion-exchange chromatography of the active fraction on DEAE-cellulose and a rechromatography on Bio-Rex 70 resin. The esterase fraction (DI-III), M(r) = 25,000 by SDS-PAGE, showed proteolytic activity on fibrinogen and casein. After 2 hr incubation, the A alpha and B beta chains of fibrinogen were intensely hydrolysed, while the gamma chain kept apparently intact, even after 20 hr of incubation. In spite of that, DI-III did not clot fibrinogen. DI-III induced edema in the rat paw. Although unable to release bradykinin, it induced contractions of the isolated rat uterus. DI-III did not catalyse the hydrolysis of bradykinin. Its arginine ester hydrolase activity was completely inhibited by diisopropyl fluorophosphate after 1 hr incubation, but not by phenylmethylsulfonyl fluoride under the same conditions. 相似文献
1000.
An improved method for deconvoluting complex spectral maps from bidimensional fluorescence monitoring is presented, relying on a combination of principal component analysis (PCA) and feedforward artificial neural networks (ANN). With the aim of reducing ANN complexity, spectral maps are first subjected to PCA, and the scores of the retained principal components are subsequently used as ANN input vector. The method is presented using the case study of an extractive membrane biofilm reactor, where fluorescence maps of a membrane-attached biofilm were analysed, which were collected under different reactor operating conditions. During ANN training, the spectral information is associated with process performance indicators. Originally, 231 excitation/emission pairs per fluorescence map were used as ANN input vector. Using PCA, each fluorescence map could be represented by a maximum of six principal components, thereby catching 99.5% of its variance. As a result, the dimension of the ANN input vector and hence the complexity of the artificial neural network was significantly reduced, and ANN training speed was increased. Correlations between principal components and ANN predicted process performance parameters were good with correlation coefficients in the order of 0.7 or higher. 相似文献