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991.
Central-place foraging seabirds increase food-loads and decrease meal frequency when they forage in areas that are distant from the breeding colony. In 2001–2002, we studied the seasonal changes in at-sea distribution, food-load mass, meal frequency, and fledging mass in rhinoceros auklets (Cerorhinca monocerata), which forage in coastal waters during the day and feed their chicks at night. In both years, greater numbers of auklets were observed flying in northern waters that are more distant from the colony in June (65 km) and July (65–66 km) than in May (38–47 km). In July of both years, many auklets flew northward across the transect set 65–120 km north of the colony at sunrise; the birds returned south again at sunset, indicating that they foraged in waters outside the study area. This seasonal northward movement of the foraging area may reflect the migration of their main prey item, the Japanese anchovy (Engraulis japonicus), which move with the Tsushima Warm Current flowing from the southern Sea of Japan. Food-load mass did not increase seasonally. In both years, the estimated daily meal frequency was lower in July than in May or June, partly because of the increased foraging distance in July. Late-hatched chicks also displayed lighter fledging masses than early chicks in both years. We suggest that late breeders are required to forage at great distances for longer periods, which may result in decreased meal frequency and lighter fledging mass of their chicks.  相似文献   
992.
We used terrestrial ecosystem models to estimate spatial and temporal variability in and uncertainty of estimated soil carbon dioxide (CO2) efflux, or soil respiration, over the Japanese Archipelago. We compared five carbon-cycle models to assess inter-model variability: Biome-BGC, CASA, LPJ, SEIB, and VISIT. These models differ in approaches to soil carbon dynamics, root respiration estimation, and relationships between decomposition and environmental factors. We simulated the carbon budget of natural ecosystems over the archipelago for 2001–2006 at 1-day time steps and 2-min (latitude and longitude) spatial resolution. The models were calibrated using measured flux data to accurately represent net ecosystem CO2 exchange. Each model successfully reproduced seasonal changes and latitudinal gradients in soil respiration. The five-model average of estimated total soil respiration of Japanese ecosystems was 295 Tg C year−1, with individual model estimates ranging from 210 to 396 Tg C year−1 (1 Tg = 1012 g). The differences between modeled estimates were more evident in summer and in warmer years, implying that they were mainly attributable to differences in modeling the temperature dependence of soil respiration. There was a large discrepancy between models in the estimated contribution of roots to total soil respiration, ranging from 3.9 to 48.4%. Although model calibration reduced the uncertainty of flux estimates, substantial uncertainties still remained in estimates of underground processes from these terrestrial carbon-cycle models.  相似文献   
993.
Mitochondrial dysfunction has long been associated with neurodegenerative disease. Therefore, mitochondrial protective agents represent a unique direction for the development of drug candidates that can modify the pathogenesis of neurodegeneration. This review discusses evidence showing that mitochondrial dysfunction has a central role in the pathogenesis of Alzheimer's, Parkinson's and Huntington's diseases and amyotrophic lateral sclerosis. We also debate the potential therapeutic efficacy of metabolic antioxidants, mitochondria-directed antioxidants and Szeto–Schiller (SS) peptides. Since these compounds preferentially target mitochondria, a major source of oxidative damage, they are promising therapeutic candidates for neurodegenerative diseases. Furthermore, we will briefly discuss the novel action of the antihistamine drug Dimebon on mitochondria.  相似文献   
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Ecosystems comprise living organisms and organic matter or detritus. In earlier community ecology theories, ecosystem dynamics were normally understood in terms of aboveground, green‐world trophic interaction networks, or food webs. Recently, there has been growing interest in the role played in ecosystem dynamics by detritus in underground, brown‐world interactions. However, the role of decomposers in the consumption of detritus to produce nutrients in ecosystem dynamics remains unclear. Here, an ecosystem model of trophic food chains, detritus, decomposers, and decomposer predators demonstrated that decomposers play a totally different role than that previously predicted, with regard to their relationship between nutrient cycling and ecosystem stability. The high flux of nutrients due to efficient decomposition by decomposers increases ecosystem stability. However, moderate levels of ecosystem openness (with movement of materials) can either greatly increase or decrease ecosystem stability. Furthermore, the stability of an ecosystem peaks at intermediate openness because open systems are less stable than closed systems. These findings suggest that decomposers and the food‐web dynamics of brown‐world interactions are crucial for ecosystem stability, and that the properties of decomposition rate and openness are important in predicting changes in ecosystem stability in response to changes in decomposition efficiency driven by climate change.  相似文献   
997.
G-protein-coupled receptors (GPCRs) are currently the most important pharmaceutical targets for drug discovery because they regulate a wide variety of physiological processes. Consequently, simple and convenient detection systems for ligands that regulate the function of GPCR have attracted attention as powerful tools for new drug development. We previously developed a yeast-based fluorescence reporter ligand detection system using flow cytometry. However, using this conventional detection system, fluorescence from a cell expressing GFP and responding to a ligand is weak, making detection of these cells by fluorescence microscopy difficult. We here report improvements to the conventional yeast fluorescence reporter assay system resulting in the development of a new highly-sensitive fluorescence reporter assay system with extremely bright fluorescence and high signal-to-noise (S/N) ratio. This new system allowed the easy detection of GPCR signaling in yeast using fluorescence microscopy. Somatostatin receptor and neurotensin receptor (implicated in Alzheimer’s disease and Parkinson’s disease, respectively) were chosen as human GPCR(s). The facile detection of binding to these receptors by cognate peptide ligands was demonstrated. In addition, we established a highly sensitive ligand detection system using yeast cell surface display technology that is applicable to peptide screening, and demonstrate that the display of various peptide analogs of neurotensin can activate signaling through the neurotensin receptor in yeast cells. Our system could be useful for identifying lead peptides with agonistic activity towards targeted human GPCR(s).  相似文献   
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Abstract

Several types of 3-deazaadenine pentofuranosides, represented by 9-(3-deoxy-β-D-glycero-pent-3-enofuranosyl)-3-deazaadenine (1), 9-(5-deoxy-β-Q-erythro-pent-4-enofuranosyl)-3-deazaadenine (2) and 9-β-D-xylo-furanosyl-3-deazaadenine (3), were prepared starting from 6-chloro-9-β-D-ribofuranosyl-3-deazaadenine (4).  相似文献   
1000.

Background

In order to improve the outcome of patients with non-small cell lung cancer (NSCLC), a biomarker that can predict the efficacy of chemotherapy is needed. The aim of this study was to assess the role of EGFR mutations and ERCC1 in predicting the efficacy of platinum-based chemotherapy and the outcome of patients with NSCLC.

Methods

We conducted a retrospective study to analyze the relationships between EGFR mutations or ERCC1 expression and progression-free survival (PFS) in patients with NSCLC who received platinum-based chemotherapy. EGFR mutation status was determined using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method, and immunohistochemistry was used to examine the expression of ERCC1 in tumor samples obtained from the patients.

Results

Among the NSCLC patients who received platinum-based chemotherapy, the median PFS was significantly better in those who had never smoked and those with exon 19 deletion, and the median overall survival (OS) was significantly better in those who had never smoked, those with exon 19 deletion, and women. Cox regression analysis revealed that exon 19 deletion and having never smoked were significantly associated with both PFS and OS. Subset analysis revealed a significant correlation between ERCC1 expression and EGFR mutation, and ERCC1-negative patients with exon 19 deletion had a longer PFS than the other patients; ERCC1-positive patients without exon 19 deletion had a shorter PFS than the other patients.

Conclusions

Our results indicate that among NSCLC patients receiving platinum-based chemotherapy, those with exon 19 deletion have a longer PFS and OS. Our findings suggest that platinum-based chemotherapy is more effective against ERCC1-negative and exon 19-positive NSCLC.  相似文献   
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