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1.
The emergence of optogenetics technology facilitated widespread applications for interrogation of complex neural networks, such as activation of specific axonal pathways, previously found impossible with electrical stimulation. Consequently, within the short period of its application in neuroscience research, optogenetics has led to findings of significant importance both during normal brain function as well as in disease. Moreover, the optimization of optogenetics for in vivo studies has allowed the control of certain behavioral responses such as motility, reflex, and sensory responses, as well as more complex emotional and cognitive behaviors such as decision-making, reward seeking, and social behavior in freely moving animals. These studies have produced a wide variety of animal models that have resulted in fundamental findings and enhanced our understanding of the neural networks associated with behavior. The increasing number of opsins available for this technique enabled even broader regulation of neuronal activity. These advancements highlight the potential of this technique for future treatment of human diseases. Here, we provide an overview of the recent developments in the field of optogenetics technology that are relevant for a better understanding of several neuropsychiatric and neurodegenerative disorders and may pave the way for future therapeutic interventions.  相似文献   
2.
The high frequency of internal structural symmetry in common protein folds is presumed to reflect their evolutionary origins from the repetition and fusion of ancient peptide modules, but little is known about the primary sequence and physical determinants of this process. Unexpectedly, a sequence and structural analysis of symmetric subdomain modules within an abundant and ancient globular fold, the β-trefoil, reveals that modular evolution is not simply a relic of the ancient past, but is an ongoing and recurring mechanism for regenerating symmetry, having occurred independently in numerous existing β-trefoil proteins. We performed a computational reconstruction of a β-trefoil subdomain module and repeated it to form a newly three-fold symmetric globular protein, ThreeFoil. In addition to its near perfect structural identity between symmetric modules, ThreeFoil is highly soluble, performs multivalent carbohydrate binding, and has remarkably high thermal stability. These findings have far-reaching implications for understanding the evolution and design of proteins via subdomain modules.  相似文献   
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We investigate the effects of spatial heterogeneity on the coexistence of competing species in the case when the heterogeneity is dynamically generated by environmental flows with chaotic mixing properties. We show that one effect of chaotic advection on the passively advected species (such as phytoplankton, or self-replicating macro-molecules) is the possibility of coexistence of more species than that limited by the number of niches they occupy. We derive a novel set of dynamical equations for competing populations.  相似文献   
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Rubinstein–Taybi syndrome (RTS) is a rare autosomal dominant congenital disorder characterized by distinctive facial features, broad thumbs and halluces, growth retardation, and a variable degree of cognitive impairment. CREBBP is the major causative gene and mutations in EP300 are the cause of RTS in a minority of patients. In this study, 17 patients with a clinical diagnosis of RTS were investigated with direct sequencing, MLPA, and array‐CGH in search for mutations in these two genes. Eleven patients (64.7%) had disease‐causing point mutations or a deletion in CREBBP and in one patient (5.9%) a causal de novo frameshift mutation in EP300 was identified. This patient had broad thumbs, mild intellectual disability, and autism. In addition, an inherited missense mutation of uncertain clinical significance was identified in EP300 in one patient and his healthy father, and three patients had intronic nucleotide changes of uncertain clinical significance in CREBBP. Snoring and sleep apnea were common in both groups and four of the patients' mothers had preeclampsia during pregnancy. Importantly, difficulties associated with anesthesia were frequently reported and included delayed or complicated emergency in 53.3% of patients.  相似文献   
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The present investigation examined the physiological parameters that contribute to 3-km running performance. Following 2 familiarization sessions, 16 experienced male triathletes (Vo(2)max = 55.7 +/- 4.9 ml.kg(-1).min(-1), age = 31.3 +/- 11.7 years) performed a 3-km time trial (3kmTT) and were assessed for selected physiological and anthropometrical characteristics. Stepwise multiple regression and correlation analysis was used to determine the variables that significantly related to 3kmTT. The analysis revealed that 82.3% of the adjusted variance in 3kmTT performance could be explained by peak treadmill running velocity during a Vo(2)max test (Vmax) alone. The addition of the running velocity at lactate threshold (LT(vel)) and peak lactate concentration ([BLa(-)](peak)) to the prediction equation allowed for 93.6% of the adjusted variance in 3kmTT to be predicted (Y = -13.64 Vmax - 25.61 LT(vel) - 5.40 [BLa(-)](peak) + 1358.5). Correlation analysis revealed that Vmax (r = -0.91), LT(vel) (r = -0.90), and Vo(2)max (r = -0.80) were significantly related to running performance. These results show that Vmax was the single best predictor of 3-km running performance in experienced male triathletes and that both aerobic and anaerobic abilities are related to improved 3kmTT performance. Since the assessment of Vmax is relatively simple to implement, we suggest that determining Vmax may be a practical method for monitoring performance changes in short-term endurance running events.  相似文献   
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Heightened interest in relevant models for human disease increases the need for improved methods for germline transgenesis. We describe a significant improvement in the creation of transgenic laboratory mice and rats by chemical modification of Sleeping Beauty transposons. Germline transgenesis in mice and rats was significantly enhanced by in vitro cytosine-phosphodiester-guanine methylation of transposons prior to injection. Heritability of transgene alleles was also greater from founder mice generated with methylated versus non-methylated transposon. The artificial methylation was reprogrammed in the early embryo, leading to founders that express the transgenes. We also noted differences in transgene insertion number and structure (single-insert versus concatemer) based on the influence of methylation and plasmid conformation (linear versus supercoiled), with supercoiled substrate resulting in efficient transpositional transgenesis (TnT) with near elimination of concatemer insertion. Combined, these substrate modifications resulted in increases in both the frequency of transgenic founders and the number of transgenes per founder, significantly elevating the number of potential transgenic lines. Given its simplicity, versatility and high efficiency, TnT with enhanced Sleeping Beauty components represents a compelling non-viral approach to modifying the mammalian germline.  相似文献   
9.
    
A comparison of two epidemiological models of immunity to malaria shows that different characterizations of immunity boosted by exposure to infection generate qualitatively different results. Attempts to control disease by reducing transmission or increasing the recovery rate can produce an increase in prevalence in the compartmental model with discrete epidemiological states. However, the parasite density always decreases in response to disease control in the model with continuous epidemiological variables. Each model accounts for some epidemiological patterns. The increase in prevalence seen in the compartmental model is in accord with observed effects of variation in transmission. Parasite suppression in areas of antimalarial drug use is consistent with the effect of an increased recovery rate in the density model. Future work should combine the two approaches, perhaps by using the compartmental model over the low to moderate range of infection rates and switching to the density model at high infection rates. In any case, the validation of models needs to take account of the usage of antimalarial drugs as well as the intensity of transmission.  相似文献   
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