全文获取类型
收费全文 | 582篇 |
免费 | 46篇 |
专业分类
628篇 |
出版年
2024年 | 2篇 |
2023年 | 4篇 |
2022年 | 10篇 |
2021年 | 22篇 |
2020年 | 10篇 |
2019年 | 14篇 |
2018年 | 16篇 |
2017年 | 13篇 |
2016年 | 30篇 |
2015年 | 36篇 |
2014年 | 32篇 |
2013年 | 32篇 |
2012年 | 47篇 |
2011年 | 42篇 |
2010年 | 28篇 |
2009年 | 14篇 |
2008年 | 36篇 |
2007年 | 29篇 |
2006年 | 19篇 |
2005年 | 28篇 |
2004年 | 22篇 |
2003年 | 34篇 |
2002年 | 14篇 |
2001年 | 11篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1989年 | 2篇 |
1988年 | 7篇 |
1987年 | 2篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1981年 | 4篇 |
1979年 | 5篇 |
1975年 | 2篇 |
1971年 | 4篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1966年 | 1篇 |
1964年 | 1篇 |
1956年 | 1篇 |
1951年 | 1篇 |
1881年 | 1篇 |
排序方式: 共有628条查询结果,搜索用时 0 毫秒
71.
The development of tolerance to a drug at the level of the neuron reflects a homeostatic mechanism by which neurons respond to perturbations of their function by external stimuli. Acute functional tolerance (AFT) to ethanol is a fast compensatory response that develops within a single drug session and normalizes neuronal function despite the continued presence of the drug. We performed a genetic screen to identify genes required for the development of acute functional tolerance to ethanol in the nematode C. elegans. We identified mutations affecting multiple genes in a genetic pathway known to regulate levels of triacylglycerols (TAGs) via the lipase LIPS-7, indicating that there is an important role for TAGs in the development of tolerance. Genetic manipulation of lips-7 expression, up or down, produced opposing effects on ethanol sensitivity and on the rate of development of AFT. Further, decreasing cholesterol levels through environmental manipulation mirrored the effects of decreased TAG levels. Finally, we found that genetic alterations in the levels of the TAG lipase LIPS-7 can modify the phenotype of gain-of-function mutations in the ethanol-inducible ion channel SLO-1, the voltage- and calcium-sensitive BK channel. This study demonstrates that the lipid milieu modulates neuronal responses to ethanol that include initial sensitivity and the development of acute tolerance. These results lend new insight into studies of alcohol dependence, and suggest a model in which TAG levels are important for the development of AFT through alterations of the action of ethanol on membrane proteins. 相似文献
72.
This paper presents an optimizing start-up strategy for a bio-methanator. The goal of the control strategy is to maximize
the outflow rate of methane in anaerobic digestion processes, which can be described by a two-population model. The methodology
relies on a thorough analysis of the system dynamics and involves the solution of two optimization problems: steady-state
optimization for determining the optimal operating point and transient optimization. The latter is a classical optimal control
problem, which can be solved using the maximum principle of Pontryagin. The proposed control law is of the bang–bang type.
The process is driven from an initial state to a small neighborhood of the optimal steady state by switching the manipulated
variable (dilution rate) from the minimum to the maximum value at a certain time instant. Then the dilution rate is set to
the optimal value and the system settles down in the optimal steady state. This control law ensures the convergence of the
system to the optimal steady state and substantially increases its stability region. The region of attraction of the steady
state corresponding to maximum production of methane is considerably enlarged. In some cases, which are related to the possibility
of selecting the minimum dilution rate below a certain level, the stability region of the optimal steady state equals the
interior of the state space. Aside its efficiency, which is evaluated not only in terms of biogas production but also from
the perspective of treatment of the organic load, the strategy is also characterized by simplicity, being thus appropriate
for implementation in real-life systems. Another important advantage is its generality: this technique may be applied to any
anaerobic digestion process, for which the acidogenesis and methanogenesis are, respectively, characterized by Monod and Haldane
kinetics. 相似文献
73.
Is the failing heart out of fuel or a worn engine running rich? A study of mitochondria in old spontaneously hypertensive rats 总被引:1,自引:0,他引:1
Jüllig M Hickey AJ Chai CC Skea GL Middleditch MJ Costa S Choong SY Philips AR Cooper GJ 《Proteomics》2008,8(12):2556-2572
Hypertension now affects about 600 million people worldwide and is a leading cause of death in the Western world. The spontaneously hypertensive rat (SHR), provides a useful model to investigate hypertensive heart failure (HF). The SHR model replicates the clinical progression of hypertension in humans, wherein early development of hypertension is followed by a long stable period of compensated cardiac hypertrophy that slowly progresses to HF. Although the hypertensive failing heart generally shows increased substrate preference towards glucose and impaired mitochondrial function, the cause-and-effect relationship between these characteristics is incompletely understood. To explore these pathogenic processes, we compared cardiac mitochondrial proteomes of 20-month-old SHR and Wistar-Kyoto controls by iTRAQ-labelling combined with multidimensional LC/MS/MS. Of 137 high-scoring proteins identified, 79 differed between groups. Changes were apparent in several metabolic pathways, chaperone and antioxidant systems, and multiple subunits of the oxidative phosphorylation complexes were increased (complexes I, III and IV) or decreased (complexes II and V) in SHR heart mitochondria. Respiration assays on skinned fibres and isolated mitochondria showed markedly lower respiratory capacity on succinate. Enzyme activity assays often also showed mismatches between increased protein expression and activities suggesting elevated protein expression may be compensatory in the face of pathological stress. 相似文献
74.
Background
Bacillus anthracis is the bacterium responsible for causing anthrax. The ability of B. anthracis to cause disease is dependent on a secreted virulence factor, lethal toxin, that promotes survival of the bacteria in the host by impairing the immune response. A well-studied effect of lethal toxin is the killing of macrophages, although the molecular mechanisms involved have not been fully characterized.Methodology/Principal Findings
Here, we demonstrate that celastrol, a quinone methide triterpene derived from a plant extract used in herbal medicine, inhibits lethal toxin-induced death of RAW264.7 murine macrophages. Celastrol did not prevent cleavage of mitogen activated protein kinase kinase 1, a cytosolic target of the toxin, indicating that it did not inhibit the uptake or catalytic activity of lethal toxin. Surprisingly, celastrol conferred almost complete protection when it was added up to 1.5 h after intoxication, indicating that it could rescue cells in the late stages of intoxication. Since the activity of the proteasome has been implicated in intoxication using other pharmacological agents, we tested whether celastrol blocked proteasome activity. We found that celastrol inhibited the proteasome-dependent degradation of proteins in RAW264.7 cells, but only slightly inhibited proteasome-mediated cleavage of fluorogenic substrates in vitro. Furthermore, celastrol blocked stimulation of IL-18 processing, indicating that celastrol acted upstream of inflammasome activation.Conclusions/Significance
This work identifies celastrol as an inhibitor of lethal toxin-mediated macrophage lysis and suggests an inhibitory mechanism involving inhibition of the proteasome pathway. 相似文献75.
G V Hillyer 《Federation proceedings》1976,35(14):2568-2571
76.
77.
Ryan A. Flynn Julia A. Belk Yanyan Qi Yuki Yasumoto Jin Wei Mia Madel Alfajaro Quanming Shi Maxwell R. Mumbach Aditi Limaye Peter C. DeWeirdt Cameron O. Schmitz Kevin R. Parker Elizabeth Woo Howard Y. Chang Tamas L. Horvath Jan E. Carette Carolyn R. Bertozzi Craig B. Wilen Ansuman T. Satpathy 《Cell》2021,184(9):2394-2411.e16
78.
Ying Wang Brian D. Carter Susan M. Gapstur Marjorie L. McCullough Mia M. Gaudet Victoria L. Stevens 《Metabolomics : Official journal of the Metabolomic Society》2018,14(10):129
Introduction
Processing delays after blood collection is a common pre-analytical condition in large epidemiologic studies. It is critical to evaluate the suitability of blood samples with processing delays for metabolomics analysis as it is a potential source of variation that could attenuate associations between metabolites and disease outcomes.Objectives
We aimed to evaluate the reproducibility of metabolites over extended processing delays up to 48 h. We also aimed to test the reproducibility of the metabolomics platform.Methods
Blood samples were collected from 18 healthy volunteers. Blood was stored in the refrigerator and processed for plasma at 0, 15, 30, and 48 h after collection. Plasma samples were metabolically profiled using an untargeted, ultrahigh performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) platform. Reproducibility of 1012 metabolites over processing delays and reproducibility of the platform were determined by intraclass correlation coefficients (ICCs) with variance components estimated from mixed-effects models.Results
The majority of metabolites (approximately 70% of 1012) were highly reproducible (ICCs?≥?0.75) over 15-, 30- or 48-h processing delays. Nucleotides, energy-related metabolites, peptides, and carbohydrates were most affected by processing delays. The platform was highly reproducible with a median technical ICC of 0.84 (interquartile range 0.68–0.93).Conclusion
Most metabolites measured by the UPLC–MS/MS platform show acceptable reproducibility up to 48-h processing delays. Metabolites of certain pathways need to be interpreted cautiously in relation to outcomes in epidemiologic studies with prolonged processing delays.79.
Length‐weight and length‐length relationships of four small fishes from the Atrai River,Dinajpur, Bangladesh 下载免费PDF全文
M. R. Islam S. Roy M. J. Mia A. K. M. Rohul Amin 《Zeitschrift fur angewandte Ichthyologie》2018,34(1):200-202
Length‐weight (LWRs) and length‐length relationships (LLRs) were determined for four fish species collected from the Atari River in Dinajpur of Bangladesh. Sampling took place monthly between January and June 2016, using seine nets of commercial fishermen (mesh size 4 mm). In LWRs (r2 > .927, p < .05), slope (b) was estimated as 3.191, 2.992, 3.217 and 3.109 for Acanthocobitis botia, Botia lohachata, Canthophrys gongota and Chanda nama, respectively. In LLRs (r2 > .812, p < .05), lengths i.e. TL, SL, HL and FL were highly correlated. The present study on these species would be the baseline for FishBase dataset. 相似文献
80.
Although numerous attempts have been made during the last five decades, no hybrids combining the qualities of the two commercially
most important species have been released so far. Dry seeds of Corchorus capsularis L. var. D-154 and Corchorus olitorius L. var. C.G. were irradiated with gamma rays of various intensities from 70 Kr. to 100 Kr. and were sown in the field. Abnormal
plants of the first generation showing bilobed and crinkled characters in their leaves induced by gamma rays were chosen as
male parents. 300 crosses of different combinations were made. In all 120 fruits developed into maturity. All the seeds failed
to germinate except those from the crosses ♀ C.G. (0 Kr.) × ♂ D-154 (80 Kr.) and ♀ D-154 (0 Kr.) × ♂ C.G. (70 Kr.). F1 plants from the cross ♀ C.G. (0 Kr.) × ♂ D-154 (80 Kr.) inherited the bilobed character of the male parent whereas the plants
from the other cross failed to show any sign of inheritance of the male parent. This indicated that the plants from the cross
♀ C.G. (0 Kr.) × ♂ D-154 (80 Kr.) were hybrids. These hybrids attained a greater height than the controls and were highly
fertile. 相似文献