全文获取类型
收费全文 | 44888篇 |
免费 | 17449篇 |
国内免费 | 80篇 |
专业分类
62417篇 |
出版年
2023年 | 54篇 |
2022年 | 79篇 |
2021年 | 488篇 |
2020年 | 2848篇 |
2019年 | 4389篇 |
2018年 | 4655篇 |
2017年 | 4624篇 |
2016年 | 4319篇 |
2015年 | 4188篇 |
2014年 | 4142篇 |
2013年 | 4525篇 |
2012年 | 3886篇 |
2011年 | 4060篇 |
2010年 | 3531篇 |
2009年 | 2382篇 |
2008年 | 2525篇 |
2007年 | 1975篇 |
2006年 | 1966篇 |
2005年 | 1637篇 |
2004年 | 1307篇 |
2003年 | 1414篇 |
2002年 | 1211篇 |
2001年 | 902篇 |
2000年 | 459篇 |
1999年 | 287篇 |
1998年 | 34篇 |
1997年 | 43篇 |
1996年 | 46篇 |
1995年 | 33篇 |
1994年 | 38篇 |
1993年 | 37篇 |
1992年 | 30篇 |
1991年 | 21篇 |
1990年 | 21篇 |
1989年 | 13篇 |
1988年 | 14篇 |
1987年 | 23篇 |
1986年 | 9篇 |
1985年 | 27篇 |
1984年 | 35篇 |
1983年 | 27篇 |
1982年 | 23篇 |
1981年 | 13篇 |
1980年 | 19篇 |
1979年 | 9篇 |
1978年 | 9篇 |
1977年 | 9篇 |
1975年 | 6篇 |
1973年 | 7篇 |
1972年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
In this work, in silico flux balance analysis is used for predicting the metabolic behavior of Streptomyces clavuligerus during clavulanic acid production. To choose the best objective function for use in the analysis, three different optimization problems are evaluated inside the flux balance analysis formulation: (i) maximization of the specific growth rate, (ii) maximization of the ATP yield, and (iii) maximization of clavulanic acid production. Maximization of ATP yield showed the best predictions for the cellular behavior. Therefore, flux balance analysis using ATP as objective function was used for analyzing different scenarios of nutrient limitations toward establishing the effect of limiting the carbon, nitrogen, phosphorous, and oxygen sources on the growth and clavulanic acid production rates. Obtained results showed that ammonia and phosphate limitations are the ones most strongly affecting clavulanic acid biosynthesis. Furthermore, it was possible to identify the ornithine flux from the urea cycle and the α‐ketoglutarate flux from the TCA cycle as the most determinant internal fluxes for promoting clavulanic acid production. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1226–1236, 2015 相似文献
82.
Jindong Zhang Vanessa Hull Zhiyun Ouyang Liang He Thomas Connor Hongbo Yang Jinyan Huang Shiqiang Zhou Zejun Zhang Caiquan Zhou Hemin Zhang Jianguo Liu 《Ecology and evolution》2017,7(8):2575-2584
The study of wildlife activity patterns is an effective approach to understanding fundamental ecological and evolutionary processes. However, traditional statistical approaches used to conduct quantitative analysis have thus far had limited success in revealing underlying mechanisms driving activity patterns. Here, we combine wavelet analysis, a type of frequency‐based time‐series analysis, with high‐resolution activity data from accelerometers embedded in GPS collars to explore the effects of internal states (e.g., pregnancy) and external factors (e.g., seasonal dynamics of resources and weather) on activity patterns of the endangered giant panda (Ailuropoda melanoleuca). Giant pandas exhibited higher frequency cycles during the winter when resources (e.g., water and forage) were relatively poor, as well as during spring, which includes the giant panda's mating season. During the summer and autumn when resources were abundant, pandas exhibited a regular activity pattern with activity peaks every 24 hr. A pregnant individual showed distinct differences in her activity pattern from other giant pandas for several months following parturition. These results indicate that animals adjust activity cycles to adapt to seasonal variation of the resources and unique physiological periods. Wavelet coherency analysis also verified the synchronization of giant panda activity level with air temperature and solar radiation at the 24‐hr band. Our study also shows that wavelet analysis is an effective tool for analyzing high‐resolution activity pattern data and its relationship to internal and external states, an approach that has the potential to inform wildlife conservation and management across species. 相似文献
83.
Saskia Vanderhaegen Marcus Fislage Katarzyna Domanska Wim Versées Els Pardon Vittorio Bellotti Jan Steyaert 《Protein science : a publication of the Protein Society》2013,22(10):1349-1357
To investigate early intermediates of β2‐microglobulin (β2m) amyloidogenesis, we solved the structure of β2m containing the amyloidogenic Pro32Gly mutation by X‐ray crystallography. One nanobody (Nb24) that efficiently blocks fibril elongation was used as a chaperone to co‐crystallize the Pro32Gly β2m monomer under physiological conditions. The complex of P32G β2m with Nb24 reveals a trans peptide bond at position 32 of this amyloidogenic variant, whereas Pro32 adopts the cis conformation in the wild‐type monomer, indicating that the cis to trans isomerization at Pro32 plays a critical role in the early onset of β2m amyloid formation. 相似文献
84.
Joshua P. Moatt Murray A. Fyfe Elizabeth Heap Luke J. M. Mitchell Fiona Moon Craig A. Walling 《Aging cell》2019,18(1)
Dietary restriction (DR) is one of the main experimental paradigms to investigate the mechanisms that determine lifespan and aging. Yet, the exact nutritional parameters responsible for DR remain unclear. Recently, the advent of the geometric framework of nutrition (GF) has refocussed interest from calories to dietary macronutrients. However, GF experiments focus on invertebrates, with the importance of macronutrients in vertebrates still widely debated. This has led to the suggestion of a fundamental difference in the mode of action of DR between vertebrates and invertebrates, questioning the suggestion of an evolutionarily conserved mechanism. The use of dietary dilution rather than restriction in GF studies makes comparison with traditional DR studies difficult. Here, using a novel nonmodel vertebrate system (the stickleback fish, Gasterosteus aculeatus), we test the effect of macronutrient versus calorie intake on key fitness‐related traits, both using the GF and avoiding dietary dilution. We find that the intake of macronutrients rather than calories determines both mortality risk and reproduction. Male mortality risk was lowest on intermediate lipid intakes, and female risk was generally reduced by low protein intakes. The effect of macronutrient intake on reproduction was similar between the sexes, with high protein intakes maximizing reproduction. Our results provide, to our knowledge, the first evidence that macronutrient, not caloric, intake predicts changes in mortality and reproduction in the absence of dietary dilution. This supports the suggestion of evolutionary conservation in the effect of diet on lifespan, but via variation in macronutrient intake rather than calories. 相似文献
85.
86.
Y.‐H. Hsu M. J. P. Simons J. Schroeder A. Girndt I. S. Winney T. Burke S. Nakagawa 《Journal of evolutionary biology》2017,30(5):951-959
Reproductive success is associated with age in many taxa, increasing in early life followed by reproductive senescence. In socially monogamous but genetically polygamous species, this generates the interesting possibility of differential trajectories of within‐pair and extra‐pair siring success with age in males. We investigate these relationships simultaneously using within‐individual analyses with 13 years of data from an insular house sparrow (Passer domesticus) population. As expected, we found that both within‐ and extra‐pair paternity success increased with age, followed by a senescence‐like decline. However, the age trajectories of within‐ and extra‐pair paternity successes differed significantly, with the extra‐pair paternity success increasing faster, although not significantly, in early life, and showing a delayed decline by 1.5 years on average later in life compared to within‐pair paternity success. These different trajectories indicate that the two alternative mating tactics should have age‐dependent pay‐offs. Males may partition their reproductive effort between within‐ and extra‐pair matings depending on their current age to reap the maximal combined benefit from both strategies. The interplay between these mating strategies and age‐specific mortality may explain the variation in rates of extra‐pair paternity observed within and between species. 相似文献
87.
Many existing methods for sustainable technical product design focus on environmental efficiency while lacking a framework for a holistic, sustainable design approach that includes combined social, technical, economic, and environmental aspects in the whole product life cycle, and that provides guidance on a technical product development level. This research proposes a framework for sustainable technical product design in the case of skis. We developed a ski under the Grown brand, benchmarked according to social, environmental, economic, and technical targets, following an initial sustainability assessment, and delivered the first environmental life cycle assessment (ELCA) and the first social life cycle assessment (SLCA) of skis. The framework applies a virtual development process as a combination of ELCA to calculate the environmental footprint as carbon equivalents of all materials and processes and a technical computer‐aided design (CAD) and computer‐aided engineering (CAE) simulation and virtual optimization using parameter studies for the nearly prototype‐free development of the benchmarked skis. The feedback loops between life cycle assessment (LCA) and virtual simulation led to the elimination of highly energy intensive materials, to the pioneering use of basalt fibers in skis, to the optimization of the use of natural materials using protective coatings from natural resins, and to the optimization of the production process. From an environmental perspective, a minimum 32% reduction in carbon equivalent emissions of materials in relation to other comparably performing skis has been achieved, as well as a pioneering step forward toward transparent communication of the environmental performance by the individual, comparable, and first published ski carbon footprint per volume unit. 相似文献
88.
El-Kabbani O Darmanin C Schneider TR Hazemann I Ruiz F Oka M Joachimiak A Schulze-Briese C Tomizaki T Mitschler A Podjarny A 《Proteins》2004,55(4):805-813
The X-ray structures of human aldose reductase holoenzyme in complex with the inhibitors Fidarestat (SNK-860) and Minalrestat (WAY-509) were determined at atomic resolutions of 0.92 A and 1.1 A, respectively. The hydantoin and succinimide moieties of the inhibitors interacted with the conserved anion-binding site located between the nicotinamide ring of the coenzyme and active site residues Tyr48, His110, and Trp111. Minalrestat's hydrophobic isoquinoline ring was bound in an adjacent pocket lined by residues Trp20, Phe122, and Trp219, with the bromo-fluorobenzyl group inside the "specificity" pocket. The interactions between Minalrestat's bromo-fluorobenzyl group and the enzyme include the stacking against the side-chain of Trp111 as well as hydrogen bonding distances with residues Leu300 and Thr113. The carbamoyl group in Fidarestat formed a hydrogen bond with the main-chain nitrogen atom of Leu300. The atomic resolution refinement allowed the positioning of hydrogen atoms and accurate determination of bond lengths of the inhibitors, coenzyme NADP+ and active-site residue His110. The 1'-position nitrogen atom in the hydantoin and succinimide moieties of Fidarestat and Minalrestat, respectively, form a hydrogen bond with the Nepsilon2 atom of His 110. For Fidarestat, the electron density indicated two possible positions for the H-atom in this bond. Furthermore, both native and anomalous difference maps indicated the replacement of a water molecule linked to His110 by a Cl-ion. These observations suggest a mechanism in which Fidarestat is bound protonated and becomes negatively charged by donating the proton to His110, which may have important implications on drug design. 相似文献
89.
Rita Mustika Arief Budiyanto Chikako Nishigori Masamitsu Ichihashi Masato Ueda 《Pigment cell & melanoma research》2005,18(1):59-62
Defects in apoptotic system may contribute in the pathogenesis and resistance of malignant melanoma cells to chemotherapy. Apoptotic protease‐activating factor‐1 (Apaf‐1) is a cell death effector that acts with cytochrome c and caspase‐9 to mediate apoptosis. Recently it was shown that metastatic melanomas often lose Apaf‐1 and are concomitantly resistant to apoptosis. It is not known, however, whether Apaf‐1 protein is lost during melanoma progression from localized to metastatic tumor. To this end, we evaluated Apaf‐1 protein expression by immunohistochemistry in 10 cases of human nevi, 11 melanomas in situ, 26 primary melanomas and 15 metastases. Significant decreases in Apaf‐1 expression was observed when comparing nevi and melanomas (chi‐square = 33.719; P < 0.0001). Moreover, primary melanomas with greater tumor thickness showed lesser expression of Apaf‐1 (chi‐square = 16.182; P < 0.003). Intriguingly, we were unable to detect Apaf‐1 expression in lesions of metastatic melanomas. These data demonstrated that there is an inverse correlation between Apaf‐1 expression and pathologic stage of melanoma. This suggests that the decreased expression of Apaf‐1 seen in correlation with melanoma progression renders melanoma more resistant to chemotherapy. 相似文献
90.
Examining the link between dietary specialization and foraging modes of stream‐dwelling brown trout Salmo trutta 下载免费PDF全文
The aim of this study was to explore differences in dietary specialization across two foraging modes (benthic v. surface‐drift foraging) of stream‐dwelling brown trout Salmo trutta. The degree of inter‐individual niche variation within each foraging mode was high, but the dietary specialization was maintained between foraging modes. This study supports the view that if aquatic invertebrates are more abundant and accessible than surface prey, the individuals will not specialize on surface prey (surface‐drift foraging). 相似文献