全文获取类型
收费全文 | 1524篇 |
免费 | 71篇 |
国内免费 | 8篇 |
专业分类
1603篇 |
出版年
2023年 | 18篇 |
2022年 | 34篇 |
2021年 | 73篇 |
2020年 | 38篇 |
2019年 | 58篇 |
2018年 | 54篇 |
2017年 | 51篇 |
2016年 | 70篇 |
2015年 | 85篇 |
2014年 | 71篇 |
2013年 | 144篇 |
2012年 | 107篇 |
2011年 | 121篇 |
2010年 | 59篇 |
2009年 | 73篇 |
2008年 | 73篇 |
2007年 | 64篇 |
2006年 | 61篇 |
2005年 | 49篇 |
2004年 | 49篇 |
2003年 | 42篇 |
2002年 | 28篇 |
2001年 | 24篇 |
2000年 | 13篇 |
1999年 | 11篇 |
1998年 | 7篇 |
1997年 | 9篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 9篇 |
1993年 | 4篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 7篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 7篇 |
1986年 | 9篇 |
1985年 | 4篇 |
1984年 | 8篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1971年 | 2篇 |
排序方式: 共有1603条查询结果,搜索用时 15 毫秒
131.
A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents. 相似文献
132.
133.
Undoubtedly, drought is one of the prime abiotic stresses in the world. Crop yield losses due to drought stress are considerable. Although a variety of approaches have been used to alleviate the problem of drought, plant breeding, either conventional breeding or genetic engineering, seems to be an efficient and economic means of tailoring crops to enable them to grow successfully in drought-prone environments. During the last century, although plant breeders have made ample progress through conventional breeding in developing drought tolerant lines/cultivars of some selected crops, the approach is, in fact, highly time-consuming and labor- and cost-intensive. Alternatively, marker-assisted breeding (MAB) is a more efficient approach, which identifies the usefulness of thousands of genomic regions of a crop under stress conditions, which was, in reality, previously not possible. Quantitative trait loci (QTL) for drought tolerance have been identified for a variety of traits in different crops. With the development of comprehensive molecular linkage maps, marker-assisted selection procedures have led to pyramiding desirable traits to achieve improvements in crop drought tolerance. However, the accuracy and preciseness in QTL identification are problematic. Furthermore, significant genetic × environment interaction, large number of genes encoding yield, and use of wrong mapping populations, have all harmed programs involved in mapping of QTL for high growth and yield under water limited conditions. Under such circumstances, a transgenic approach to the problem seems more convincing and practicable, and it is being pursued vigorously to improve qualitative and quantitative traits including tolerance to biotic and abiotic stresses in different crops. Rapid advance in knowledge on genomics and proteomics will certainly be beneficial to fine-tune the molecular breeding and transformation approaches so as to achieve a significant progress in crop improvement in future. Knowledge of gene regulation and signal transduction to generate drought tolerant crop cultivars/lines has been discussed in the present review. In addition, the advantages and disadvantages as well as future prospects of each breeding approach have also been discussed. 相似文献
134.
The recent interest in using microorganisms for biofuels is motivation enough to study bioconvection and cell dispersion in tubes subject to imposed flow. To optimize light and nutrient uptake, many microorganisms swim in directions biased by environmental cues (e.g. phototaxis in algae and chemotaxis in bacteria). Such taxes inevitably lead to accumulations of cells, which, as many microorganisms have a density different to the fluid, can induce hydrodynamic instabilites. The large-scale fluid flow and spectacular patterns that arise are termed bioconvection. However, the extent to which bioconvection is affected or suppressed by an imposed fluid flow and how bioconvection influences the mean flow profile and cell transport are open questions. This experimental study is the first to address these issues by quantifying the patterns due to suspensions of the gravitactic and gyrotactic green biflagellate alga Chlamydomonas in horizontal tubes subject to an imposed flow. With no flow, the dependence of the dominant pattern wavelength at pattern onset on cell concentration is established for three different tube diameters. For small imposed flows, the vertical plumes of cells are observed merely to bow in the direction of flow. For sufficiently high flow rates, the plumes progressively fragment into piecewise linear diagonal plumes, unexpectedly inclined at constant angles and translating at fixed speeds. The pattern wavelength generally grows with flow rate, with transitions at critical rates that depend on concentration. Even at high imposed flow rates, bioconvection is not wholly suppressed and perturbs the flow field. 相似文献
135.
136.
137.
Al-Madhoun AS Eriksson S Wang ZX Naimi E Knaus EE Wiebe LI 《Nucleosides, nucleotides & nucleic acids》2004,23(12):1865-1874
The thymidine mimics isocarbostyril nucleosides and difluorophenyl nucleosides were tested as deoxynucleoside kinase substrates using recombinant human cytosolic thymidine kinase (TK1) and deoxycytidine kinase (dCK), and mitochondrial thymidine kinase (TK2) and deoxyguanosine kinase (dGK). The isocarbostyril nucleoside compound 1-(2-deoxy-beta-D-ribofuranosyl)-isocarbostyril (EN1) was a poor substrate with all the enzymes. The phosphorylation rates of EN1 with TK1 and TK2 were <1% relative to Thd, where as the phosphorylation rates for EN1 were 1.4% and 1.1% with dCK and dGK relative to dCyd and dGuo, respectively. The analogue 1-(2-deoxy-beta-D-ribofuranosyl)-7-iodoisocarbostyril (EN2) showed poor relative-phosphorylation efficiencies (kcat/Km) with both TK1 and dGK, but not with TK2. The kcat/Km value for EN2 with TK2 was 12.6% relative to that for Thd. Of the difluorophenyl nucleosides, 5-(1'-(2'-deoxy-beta-D-ribofuranosyl))-2,4-difluorotoluene (JW1) and 1-(1'-(2'-deoxy-beta-D-ribofuranosyl))-2,4-difluoro-5-iodobenzene (JW2) were substrates for TK1 with phosphorylation efficiencies of about 5% relative to that for Thd. Both analogues were considerably more efficient substrates for TK2, with kcat/Km values of 45% relative to that for Thd. 2,5-Difluoro-4-[1-(2-deoxy-beta-L-ribofuranosyl)]-aniline (JW5), a L-nucleoside mimic, was phosphorylated up to 15% as efficiently as deoxycytidine by dCK. These data provide a possible explanation for the previously reported lack of cytotoxicity of the isocarbostyril- and difluorophenyl nucleosides, but potential mitochondrial effects of EN2, JW1 and JW2 should be further investigated. 相似文献
138.
Sulfate reduction, methanogenesis, and methane oxidation in the upper sediments of the Vistula and Curonian Lagoons, Baltic Sea 总被引:1,自引:0,他引:1
N. V. Pimenov M. O. Ul’yanova T. A. Kanapatskii I. N. Mitskevich I. I. Rusanov P. A. Sigalevich I. A. Nemirovskaya V. V. Sivkov 《Microbiology》2013,82(2):224-233
Microbiological, biogeochemical, and isotope geochemical investigations of the upper sediments of the Vistula and Curonian lagoons, Baltic Sea, were carried out. High content of organic matter in the sediments was responsible for the high numbers (over 1010 cells cm?3) and activity of heterotrophic microorganisms. The calculated integral rates of dark CO2 assimilation for the upper 30 cm of the sediments varied 12.5 to 38.8 mmol m?2 day?1 and were somewhat higher in the Curonian Lagoon than in the Vistula Lagoon. Integral rates of sulfate reduction were higher in the more saline Vistula Lagoon. Rapid consumption of sulfates of the pore water resulted in intensified methanogenesis, with significantly higher rates detected in the silts of the Curonian Lagoon. High rates of methanogenesis in the Curonian Lagoon correlated with higher methane levels in its upper sediments and near-bottom water. The highest rates of methane oxidation were detected in the uppermost sediment horizons (oxidized or slightly reduced), which was an indication of the barrier role of aerobic methanotrophic bacteria. The calculated methane flows from the sediments into the water column were 0.45 and 0.007 mmol m?2 day?1 for the Vistula and Curonian Lagoons, respectively. Low methane flow from the sediments of the Curonian Lagoon resulted probably from the specific weather (wind) conditions during sampling. The near-stormy conditions in the Curonian Lagoon caused sediment detachment, resulting in methane release into the water column. 相似文献
139.
140.
Ahmed Aboul-Fotouh Mourad Seikou Nakamura Tsubasa Ueno Takahiro Minami Takanari Yagi Haruka Yasue Ryoko Komatsu Masayuki Yoshikawa Ashraf Mohamed Taye Mohamed Ahmed El-Moselhy Mohamed Montaser Khalifa Hisashi Matsuda 《Bioorganic & medicinal chemistry letters》2013,23(17):4813-4816
In a previous study, retrofractamide A from the fruit of Piper chaba was shown to promote adipogenesis in 3T3-L1 cells. In the present study, retrofractamide A and its derivatives were synthesized, and their adipogenetic effects in 3T3-L1 cells were examined. Among the tested compounds, an amide composed of 9-(3′,4′-methylenedioxyphenyl)-nona-2E,4E,8E-trienoic acid and an n-butyl or n-pentyl amine showed strongest activity. Moreover, the amide with the n-pentyl amine moiety significantly increased the uptake of 2-deoxyglucose into the cells, and also increased the mRNA levels of adiponectin, peroxisome proliferator-activated receptor γ2 (PPARγ2), glucose transporter 4 (GLUT4), fatty acid-binding protein (aP2), and CCAAT/enhancer-binding protein (C/EBP) α and β in a similar manner as the PPARγ agonist troglitazone, although it had less agonistic activity against PPARγ. 相似文献