首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   2880篇
  免费   190篇
  2022年   17篇
  2021年   26篇
  2020年   27篇
  2019年   25篇
  2018年   36篇
  2017年   40篇
  2016年   50篇
  2015年   78篇
  2014年   105篇
  2013年   137篇
  2012年   162篇
  2011年   160篇
  2010年   115篇
  2009年   116篇
  2008年   153篇
  2007年   135篇
  2006年   134篇
  2005年   135篇
  2004年   159篇
  2003年   157篇
  2002年   116篇
  2001年   92篇
  2000年   71篇
  1999年   63篇
  1998年   53篇
  1997年   36篇
  1996年   40篇
  1995年   33篇
  1994年   34篇
  1993年   50篇
  1992年   47篇
  1991年   46篇
  1990年   42篇
  1989年   36篇
  1988年   22篇
  1987年   33篇
  1986年   34篇
  1985年   23篇
  1984年   17篇
  1983年   19篇
  1982年   17篇
  1981年   19篇
  1980年   12篇
  1979年   20篇
  1978年   12篇
  1977年   16篇
  1975年   11篇
  1974年   13篇
  1973年   14篇
  1972年   12篇
排序方式: 共有3070条查询结果,搜索用时 15 毫秒
971.
Evasion of gaseous carbon (C) from streams is often poorly quantified in landscape C budgets. Even though the potential importance of the capillary network of streams as C conduits across the land–water–atmosphere interfaces is sometimes mentioned, low‐order streams are often left out of budget estimates due to being poorly characterized in terms of gas exchange and even areal surface coverage. We show that evasion of C is greater than all the total dissolved C (both organic and inorganic) exported downstream in the waters of a boreal landscape. In this study evasion of carbon dioxide (CO2) from running waters within a 67 km2 boreal catchment was studied. During a 4 year period (2006–2009) 13 streams were sampled on 104 different occasions for dissolved inorganic carbon (DIC) and dissolved organic carbon (DOC). From a locally determined model of gas exchange properties, we estimated the daily CO2 evasion with a high‐resolution (5 × 5 m) grid‐based stream evasion model comprising the entire ~100 km stream network. Despite the low areal coverage of stream surface, the evasion of CO2 from the stream network constituted 53% (5.0 (±1.8) g C m?2 yr?1) of the entire stream C flux (9.6 (±2.4) g C m?2 yr?1) (lateral as DIC, DOC, and vertical as CO2). In addition, 72% of the total CO2 loss took place already in the first‐ and second‐order streams. This study demonstrates the importance of including CO2 evasion from low‐order boreal streams into landscape C budgets as it more than doubled the magnitude of the aquatic conduit for C from this landscape. Neglecting this term will consequently result in an overestimation of the terrestrial C sink strength in the boreal landscape.  相似文献   
972.
A program for numerical simulation of a whole ski race, from start to finish, is developed in MATLAB. The track is modelled by a set of cubical splines in two dimensions and can be used to simulate a track in a closed loop or with the start and finish at different locations. The forces considered in the simulations are gravitational force, normal force between snow and skis, drag force from the wind, frictional force between snow and ski and driving force from the skier. The differential equations of motion are solved from start to finish with the Runge–Kutta method. Different wind situations during the race can be modelled, as well as different glide conditions on different parts of the track. It is also possible to vary the available power during the race. The simulation program's output is the total time of the race, together with the forces and speed during different parts of the race and intermediate times at selected points. Some preliminary simulations are also presented.  相似文献   
973.

Background

Although aberrant DNA methylation has been observed previously in acute lymphoblastic leukemia (ALL), the patterns of differential methylation have not been comprehensively determined in all subtypes of ALL on a genome-wide scale. The relationship between DNA methylation, cytogenetic background, drug resistance and relapse in ALL is poorly understood.

Results

We surveyed the DNA methylation levels of 435,941 CpG sites in samples from 764 children at diagnosis of ALL and from 27 children at relapse. This survey uncovered four characteristic methylation signatures. First, compared with control blood cells, the methylomes of ALL cells shared 9,406 predominantly hypermethylated CpG sites, independent of cytogenetic background. Second, each cytogenetic subtype of ALL displayed a unique set of hyper- and hypomethylated CpG sites. The CpG sites that constituted these two signatures differed in their functional genomic enrichment to regions with marks of active or repressed chromatin. Third, we identified subtype-specific differential methylation in promoter and enhancer regions that were strongly correlated with gene expression. Fourth, a set of 6,612 CpG sites was predominantly hypermethylated in ALL cells at relapse, compared with matched samples at diagnosis. Analysis of relapse-free survival identified CpG sites with subtype-specific differential methylation that divided the patients into different risk groups, depending on their methylation status.

Conclusions

Our results suggest an important biological role for DNA methylation in the differences between ALL subtypes and in their clinical outcome after treatment.  相似文献   
974.
Specific Se-metabolites have been recognized to be the main elements responsible for beneficial effects of Se-enriched diet, and Se-methylselenocysteine (SeMCys) is thought to be among the most effective ones. Here we show that an engineered Saccharomyces cerevisiae strain, expressing a codon optimized heterologous selenocysteine methyltransferase and endowed with high intracellular levels of S-adenosyl-methionine, was able to accumulate SeMCys at levels higher than commercial selenized yeasts. A fine tuned carbon- and sulfate-limited fed-batch bioprocess was crucial to achieve good yields of biomass and SeMCys. Through the coupling of metabolic and bioprocess engineering we achieved a ~24-fold increase in SeMCys, compared to certified reference material of selenized yeast. In addition, we investigated the interplay between sulfur and selenium metabolism and the possibility that redox imbalance occurred along with intracellular accumulation of Se. Collectively, our data show how the combination of metabolic and bioprocess engineering can be used for the production of selenized yeast enriched with beneficial Se-metabolites.  相似文献   
975.
A program for numerical simulation of a whole ski race, from start to finish, is developed in MATLAB. The track is modelled by a set of cubical splines in two dimensions and can be used to simulate a track in a closed loop or with the start and finish at different locations. The forces considered in the simulations are gravitational force, normal force between snow and skis, drag force from the wind, frictional force between snow and ski and driving force from the skier. The differential equations of motion are solved from start to finish with the Runge-Kutta method. Different wind situations during the race can be modelled, as well as different glide conditions on different parts of the track. It is also possible to vary the available power during the race. The simulation program's output is the total time of the race, together with the forces and speed during different parts of the race and intermediate times at selected points. Some preliminary simulations are also presented.  相似文献   
976.
977.
The development of non‐fullerene‐based electron acceptors (especially organic molecules with sufficient absorption property within the solar spectrum region) for bulk‐heterojunction (BHJ) organic solar cells (OSCs) is an important issue for the achievement of high photoconversion efficiency. In this contribution, a new class of organic acceptors di‐cyan substituted quinacridone derivatives (DCN‐nCQA, n = 4, 6 and 8) for BHJ solar cells was designed and synthesized. DCN‐nCQA molecules possess facile synthesis, solution processability, visible and near‐IR light absorption and relatively stable characteristics. The DCN‐8CQA molecule exhibited a proper LUMO energy level (–4.1 eV), small bandgap (1.8 eV) and moderate electron mobility (10?4 cm2 V?1 S?1), suggesting that this molecule is an ideal acceptor material for the classical donor material regio‐regular poly (3‐hexylthiophene) (P3HT). A photovoltaic device with a structure of [ITO/PEDOT:PSS/P3HT:DCN‐8CQA/LiF/Al] displayed a power conversion efficiency of 1.57% and a fill factor of 57% under 100 mW cm?2 AM 1.5G simulated solar illumination. The DCN‐nCQA molecules showed remarkable absorption in the region from 650 to 700 nm, where P3HT has a weak absorption promoting overlap with the solar spectrum and potentially improving the performance of the solar cell.  相似文献   
978.
Because of apparent reproductive isolation between Northern and Southern hemisphere populations of the black drum Pogonius cromis, we tested the hypothesis that advertisement calls from a southern population would differ from known calls of North American populations. Additionally, we quantified disturbance and advertisement calls, their changes with fish size and sex, not previously examined in this species. Unlike most sciaenids, both sexes of P. cromis possess robust sonic muscles, and both produce disturbance calls when handled. However, only males produce an advertisement call used in courtship. The disturbance call consists of a variable train of short-duration pulses (average 23?ms). The duration, interpulse interval, and dominant frequency of pulses are similar in males and females and change developmentally: pulse duration and interpulse interval increase and dominant frequency decreases with fish size. Advertisement calls, recorded in the field and in captivity, are long-duration (average 184?ms) and tonal. Based on variation in fundamental frequency, which decreases with fish size, field choruses are composed of different-sized individuals. The duration of advertisement calls, about a third of those from Florida populations, suggests genetic differentiation between northern and southern populations.  相似文献   
979.
Sera from 25 metastatic breast cancer patients and 25 healthy controls were subjected to affinity chromatography using immobilized galectin-1. Serum from the healthy subjects contained on average 1.2 mg per ml (range 0.7-2.2) galectin-1 binding glycoproteins, whereas serum from the breast cancer patients contained on average 2.2 mg/ml (range 0.8-3.9), with a higher average for large primary tumours. The major bound glycoproteins were α-2-macroglobulin, IgM and haptoglobin. Both the IgM and haptoglobin concentrations were similar in cancer compared to control sera, but the percentage bound to galectin-1 was lower for IgM and higher for haptoglobin: about 50% (range 20-80) in cancer sera and about 30% (range 25-50) in healthy sera. Galectin-1 binding and non-binding fractions were separated by affinity chromatography from pooled haptoglobin from healthy sera. The N-glycans of each fraction were analyzed by mass spectrometry, and the structural differences and galectin-1 mutants were used to identify possible galectin-1 binding sites. Galectin-1 binding and non-binding fractions were also analyzed regarding their haptoglobin function. Both were similar in forming complex with haemoglobin and mediate its uptake into alternatively activated macrophages. However, after uptake there was a dramatic difference in intracellular targeting, with the galectin-1 non-binding fraction going to a LAMP-2 positive compartment (lysosomes), while the galectin-1 binding fraction went to larger galectin-1 positive granules. In conclusion, galectin-1 detects a new type of functional biomarker for cancer: a specific type of glycoform of haptoglobin, and possibly other serum glycoproteins, with a different function after uptake into tissue cells.  相似文献   
980.
We have developed an approach for simultaneous detection of individual endogenous protein modifications and mRNA molecules in single cells in situ. For this purpose we combined two methods previously developed in our lab: in situ proximity ligation assay for the detection of individual protein interactions and -modifications and in situ detection of single mRNA molecules using padlock probes. As proof-of-principle, we demonstrated the utility of the method for simultaneous detection of phosphorylated PDGFRβ and DUSP6/MKP-3 mRNA molecules in individual human fibroblasts upon PDGF-BB stimulation. Further we applied drugs disrupting the PDGFRβ signaling pathway at various sites to show that this combined method can concurrently monitor the molecular effect of the drugs, i.e. inhibition of downstream signaling from the targeted node in the signaling pathway. Due to its ability to detect different types of molecules in single cells in situ the method presented here can contribute to a deeper understanding of cell-to-cell variations and can be applied to e.g. pinpoint effector sites of drugs in a signaling pathway.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号