全文获取类型
收费全文 | 1358篇 |
免费 | 68篇 |
国内免费 | 1篇 |
专业分类
1427篇 |
出版年
2023年 | 3篇 |
2022年 | 7篇 |
2021年 | 27篇 |
2020年 | 19篇 |
2019年 | 24篇 |
2018年 | 43篇 |
2017年 | 35篇 |
2016年 | 47篇 |
2015年 | 53篇 |
2014年 | 68篇 |
2013年 | 102篇 |
2012年 | 115篇 |
2011年 | 115篇 |
2010年 | 67篇 |
2009年 | 45篇 |
2008年 | 90篇 |
2007年 | 115篇 |
2006年 | 88篇 |
2005年 | 83篇 |
2004年 | 55篇 |
2003年 | 66篇 |
2002年 | 53篇 |
2001年 | 11篇 |
2000年 | 3篇 |
1999年 | 7篇 |
1998年 | 7篇 |
1997年 | 8篇 |
1996年 | 11篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1991年 | 2篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1982年 | 3篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1971年 | 2篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有1427条查询结果,搜索用时 15 毫秒
991.
Niall Browne Frauke Hackenberg Wojciech Streciwilk Matthias Tacke Kevin Kavanagh 《Biometals》2014,27(4):745-752
The antimicrobial drug candidate 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate (SBC3) was evaluated for its ability to function in vivo using larvae of Galleria mellonella. A SBC3 concentration of 25 μg/ml inhibited the growth of Staphylococcus aureus by 71.2 % and Candida albicans by 86.2 % in vitro. Larvae inoculated with 20 μl of SBC3 solution showed no ill effects up to a concentration of 250 μg/ml but administration of 500 μg/ml resulted in a 40 % reduction in larval survival and administration of a dose of 1,000 μg/ml resulted in total larval death at 24 h. Larvae inoculated with S. aureus or C. albicans and subsequently administered SBC3 showed increased survival. Administration of SBC3 to larvae did not boost the insect immune response as indicated by lack of an increase in the density of circulating haemocytes (immune cells). The abundance of a number of proteins involved in the insect immune response was reduced in larvae that received 20 μl SBC3 solution of 100 μg/ml. This is the first demonstration of the in vivo activity of SBC3 against S. aureus and C. albicans and demonstrates that SBC3 does not stimulate a non-specific immune response in larvae. 相似文献
992.
Cristina Cvitanich Wojciech J Przybyłowicz Dorian F Urbanski Anna M Jurkiewicz Jolanta Mesjasz-Przybyłowicz Matthew W Blair Carolina Astudillo Erik Ø Jensen Jens Stougaard 《BMC plant biology》2010,10(1):26
Background
Iron is an important micronutrient for all living organisms. Almost 25% of the world population is affected by iron deficiency, a leading cause of anemia. In plants, iron deficiency leads to chlorosis and reduced yield. Both animals and plants may suffer from iron deficiency when their diet or environment lacks bioavailable iron. A sustainable way to reduce iron malnutrition in humans is to develop staple crops with increased content of bioavailable iron. Knowledge of where and how iron accumulates in seeds of crop plants will increase the understanding of plant iron metabolism and will assist in the production of staples with increased bioavailable iron. 相似文献993.
Maintenance of replication fork stability is of utmost importance for dividing cells to preserve viability and prevent disease. The processes involved not only ensure faithful genome duplication in the face of endogenous and exogenous DNA damage but also prevent genomic instability, a recognized causative factor in tumor development. Here, we describe a simple and cost-effective fluorescence microscopy-based method to visualize DNA replication in the avian B-cell line DT40. This cell line provides a powerful tool to investigate protein function in vivo by reverse genetics in vertebrate cells(1). DNA fiber fluorography in DT40 cells lacking a specific gene allows one to elucidate the function of this gene product in DNA replication and genome stability. Traditional methods to analyze replication fork dynamics in vertebrate cells rely on measuring the overall rate of DNA synthesis in a population of pulse-labeled cells. This is a quantitative approach and does not allow for qualitative analysis of parameters that influence DNA synthesis. In contrast, the rate of movement of active forks can be followed directly when using the DNA fiber technique(2-4). In this approach, nascent DNA is labeled in vivo by incorporation of halogenated nucleotides (Fig 1A). Subsequently, individual fibers are stretched onto a microscope slide, and the labeled DNA replication tracts are stained with specific antibodies and visualized by fluorescence microscopy (Fig 1B). Initiation of replication as well as fork directionality is determined by the consecutive use of two differently modified analogues. Furthermore, the dual-labeling approach allows for quantitative analysis of parameters that influence DNA synthesis during the S-phase, i.e. replication structures such as ongoing and stalled forks, replication origin density as well as fork terminations. Finally, the experimental procedure can be accomplished within a day, and requires only general laboratory equipment and a fluorescence microscope. 相似文献
994.
Longidorus poessneckensis Altherr, 1974 and L. piceicola Lišková, Robbins & Brown, 1997 (Nematoda: Longidoridae) represent new records from Poland. These two species are described
and illustrated together with a male and bivulval female of L. poessneckensis. In its general morphology and morphometrics, the male of L. poessneckensis is similar to the females, but has a spicule 100 μm long and one adanal pair, two double and a row of six single ventromedian
supplements. Comments on the differential diagnosis of L. poessneckensis and two morphologically related species, L. uroshis Krnjaić, Lamberti, Krnjaić, Agostinelli & Radicci, 2000 and L. macrosoma Hooper, 1961 are given. 相似文献
995.
996.
Renata Studziska Renata Koodziejska Wojciech Paziski Daria Kupczyk Tomasz Kosmalski Katarzyna Jasieniecka Boena Modzelewska‐Banachiewicz 《化学与生物多样性》2019,16(6)
11β‐Hydroxysteroid dehydrogenase type 1 (11β‐HSD1) is an enzyme that affects the body's cortisol levels. The inhibition of its activity can be used in the treatment of Cushing's syndrome, metabolic syndrome and type 2 diabetes. In this study, we synthesized new derivatives of 2‐(methylamino)thiazol‐4(5H)‐one and tested their activity towards inhibition of 11β‐HSD1 and its isoform – 11β‐HSD2. The results were compared with the previously tested allyl derivatives. We found out that methyl derivatives are weaker inhibitors of 11β‐HSD1 in comparison to their allyl analogs. Due to significant differences in the activity of the compounds, molecular modeling was performed, which was aimed at comparing the interactions between 11β‐HSD1 and ligands differing by substituent at the amine group (allyl vs. methyl). Modeling showed that the absence of the allyl group can lead to the rotation of whole ligand molecule which affects its interaction with the enzyme. 相似文献
997.
Helen E. Roy Sven Bacher Franz Essl Tim Adriaens David C. Aldridge John D. D. Bishop Tim M. Blackburn Etienne Branquart Juliet Brodie Carles Carboneras Elizabeth J. Cottier-Cook Gordon H. Copp Hannah J. Dean Jrgen Eilenberg Belinda Gallardo Mariana Garcia Emili García‐Berthou Piero Genovesi Philip E. Hulme Marc Kenis Francis Kerckhof Marianne Kettunen Dan Minchin Wolfgang Nentwig Ana Nieto Jan Pergl Oliver L. Pescott Jodey M. Peyton Cristina Preda Alain Roques Steph L. Rorke Riccardo Scalera Stefan Schindler Karsten Schnrogge Jack Sewell Wojciech Solarz Alan J. A. Stewart Elena Tricarico Sonia Vanderhoeven Gerard van der Velde Montserrat Vil Christine A. Wood Argyro Zenetos Wolfgang Rabitsch 《Global Change Biology》2019,25(3):1032-1048
The European Union (EU) has recently published its first list of invasive alien species (IAS) of EU concern to which current legislation must apply. The list comprises species known to pose great threats to biodiversity and needs to be maintained and updated. Horizon scanning is seen as critical to identify the most threatening potential IAS that do not yet occur in Europe to be subsequently risk assessed for future listing. Accordingly, we present a systematic consensus horizon scanning procedure to derive a ranked list of potential IAS likely to arrive, establish, spread and have an impact on biodiversity in the region over the next decade. The approach is unique in the continental scale examined, the breadth of taxonomic groups and environments considered, and the methods and data sources used. International experts were brought together to address five broad thematic groups of potential IAS. For each thematic group the experts first independently assembled lists of potential IAS not yet established in the EU but potentially threatening biodiversity if introduced. Experts were asked to score the species within their thematic group for their separate likelihoods of i) arrival, ii) establishment, iii) spread, and iv) magnitude of the potential negative impact on biodiversity within the EU. Experts then convened for a 2‐day workshop applying consensus methods to compile a ranked list of potential IAS. From an initial working list of 329 species, a list of 66 species not yet established in the EU that were considered to be very high (8 species), high (40 species) or medium (18 species) risk species was derived. Here, we present these species highlighting the potential negative impacts and the most likely biogeographic regions to be affected by these potential IAS. 相似文献
998.
999.
Pashkov V Huang J Parameswara VK Kedzierski W Kurrasch DM Tall GG Esser V Gerard RD Uyeda K Towle HC Wilkie TM 《The Journal of biological chemistry》2011,286(17):15116-15125
1000.
Augustyniak W Brzezinska AA Pijning T Wienk H Boelens R Dijkstra BW Reetz MT 《Protein science : a publication of the Protein Society》2012,21(4):487-497
Previously, Lipase A from Bacillus subtilis was subjected to in vitro directed evolution using iterative saturation mutagenesis, with randomization sites chosen on the basis of the highest B-factors available from the crystal structure of the wild-type (WT) enzyme. This provided mutants that, unlike WT enzyme, retained a large part of their activity after heating above 65 °C and cooling down. Here, we subjected the three best mutants along with the WT enzyme to biophysical and biochemical characterization. Combining thermal inactivation profiles, circular dichroism, X-ray structure analyses and NMR experiments revealed that mutations of surface amino acid residues counteract the tendency of Lipase A to undergo precipitation under thermal stress. Reduced precipitation of the unfolding intermediates rather than increased conformational stability of the evolved mutants seems to be responsible for the activity retention. 相似文献