全文获取类型
收费全文 | 1449篇 |
免费 | 125篇 |
国内免费 | 1篇 |
出版年
2023年 | 13篇 |
2022年 | 31篇 |
2021年 | 72篇 |
2020年 | 35篇 |
2019年 | 43篇 |
2018年 | 61篇 |
2017年 | 26篇 |
2016年 | 64篇 |
2015年 | 87篇 |
2014年 | 115篇 |
2013年 | 106篇 |
2012年 | 118篇 |
2011年 | 124篇 |
2010年 | 81篇 |
2009年 | 71篇 |
2008年 | 79篇 |
2007年 | 75篇 |
2006年 | 73篇 |
2005年 | 55篇 |
2004年 | 51篇 |
2003年 | 57篇 |
2002年 | 42篇 |
2001年 | 8篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 4篇 |
1997年 | 6篇 |
1996年 | 8篇 |
1995年 | 5篇 |
1994年 | 9篇 |
1992年 | 2篇 |
1988年 | 3篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1979年 | 2篇 |
1976年 | 2篇 |
1972年 | 2篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1965年 | 1篇 |
1962年 | 1篇 |
1961年 | 1篇 |
1946年 | 1篇 |
1943年 | 2篇 |
1926年 | 1篇 |
1924年 | 1篇 |
1923年 | 1篇 |
1909年 | 1篇 |
1902年 | 2篇 |
1862年 | 1篇 |
排序方式: 共有1575条查询结果,搜索用时 78 毫秒
171.
Braulio Insuasty Alexis Tigreros Fabián Orozco Jairo Quiroga Rodrigo Abonía Manuel Nogueras Adolfo Sanchez Justo Cobo 《Bioorganic & medicinal chemistry》2010,18(14):4965-4974
Novel (E)-1-aryl-3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-ones 5/6 (pyrazolic chalcones) were synthesized from a Claisen–Schmidt reaction of 3-aryl-1-phenylpyrazol-4-carboxaldehydes 4 with several acetophenone derivatives 1. Subsequently, the microwave-assisted cyclocondensation reaction of chalcones 5/6 with hydrazine afforded the new racemic 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazoles 7 or their N-acetyl derivatives 8 and 9 when reactions where carried out in DMF or acetic acid, respectively. Several of these compounds were screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where 5c and 9g showed remarkable activity mainly against leukemia (K-562 and SR), renal cancer (UO-31) and non-small cell lung cancer (HOP-92) cell lines, with the most important GI50 values ranging from 0.04 to 11.4 μM, from the in vitro assays. 相似文献
172.
Graham F. Hatfull Deborah Jacobs-Sera Welkin H. Pope Ching-Chung Ko Manisha C. Patel Robert H. Edgar Charles A. Bowman Elizabeth C. Paladin Alexis L. Smith Thuy T. Pham Amy M. Vogelsberger Jessica L. Wynalek Matt W. Bogel Steven G. Cresawn 《Journal of molecular biology》2010,397(1):119-221
Mycobacteriophages are viruses that infect mycobacterial hosts. Expansion of a collection of sequenced phage genomes to a total of 60—all infecting a common bacterial host—provides further insight into their diversity and evolution. Of the 60 phage genomes, 55 can be grouped into nine clusters according to their nucleotide sequence similarities, 5 of which can be further divided into subclusters; 5 genomes do not cluster with other phages. The sequence diversity between genomes within a cluster varies greatly; for example, the 6 genomes in Cluster D share more than 97.5% average nucleotide similarity with one another. In contrast, similarity between the 2 genomes in Cluster I is barely detectable by diagonal plot analysis. In total, 6858 predicted open-reading frames have been grouped into 1523 phamilies (phams) of related sequences, 46% of which possess only a single member. Only 18.8% of the phams have sequence similarity to non-mycobacteriophage database entries, and fewer than 10% of all phams can be assigned functions based on database searching or synteny. Genome clustering facilitates the identification of genes that are in greatest genetic flux and are more likely to have been exchanged horizontally in relatively recent evolutionary time. Although mycobacteriophage genes exhibit a smaller average size than genes of their host (205 residues compared with 315), phage genes in higher flux average only 100 amino acids, suggesting that the primary units of genetic exchange correspond to single protein domains. 相似文献
173.
Alexis S. Chaine Nicolas Schtickzelle Thierry Polard Michèle Huet Jean Clobert 《Evolution; international journal of organic evolution》2010,64(5):1290-1300
Aggregative groups entail costs that must be overcome for the evolution of complex social interactions. Understanding the mechanisms that allow aggregations to form and restrict costs of cheating can provide a resolution to the instability of social evolution. Aggregation in Tetrahymena thermophila is associated with costs of reduced growth and benefits of improved survival through “growth factor” exchange. We investigated what mechanisms contribute to stable cooperative aggregation in the face of potential exploitation by less‐cooperative lines using experimental microcosms. We found that kin recognition modulates aggregative behavior to exclude cheaters from social interactions. Long‐distance kin recognition across patches modulates social structure by allowing recruitment of kin in aggregative lines and repulsion in asocial lines. Although previous studies have shown a clear benefit to social aggregation at low population densities, we found that social aggregation has very different effects at higher densities. Lower growth rates are a cost of aggregation, but also present potential benefits when restricted to kin aggregations: slow growth and crowd tolerance allow aggregations to form and permit longer persistence on ephemeral resources. Thus in highly dynamic metapopulations, kin recognition plays an important role in the formation and stability of social groups that increase persistence through cooperative consumptive restraint. 相似文献
174.
Marcil M Bourduas K Ascah A Burelle Y 《American journal of physiology. Heart and circulatory physiology》2006,290(4):H1549-H1557
The purpose of this study was to determine whether regular exercise (treadmill running, 10 wk) alters the susceptibility of rat isolated heart mitochondria to Ca(2+)-induced permeability transition pore (PTP) opening and whether this could be associated with changes in the modulation of PTP opening by selected physiological effectors. Basal leak-driven and ADP-stimulated respiration in the presence of substrates for complex I, II, and IV were not affected by training. Fluorimetric studies revealed that in the control and exercise-trained groups, the amount of Ca(2+) required to trigger PTP opening was greater in the presence of complex II vs. I substrates (230 +/- 12 vs. 134 +/- 7 nmol Ca(2+)/mg protein, P < 0.01; pooled average of control and trained groups). In addition, with a substrate feeding the complex II, training increased by 45% (P < 0.01) the amount of Ca(2+) required to trigger PTP opening both in the presence and absence of the PTP inhibitor cyclosporin A. However, membrane potential, reactive oxygen species production, NAD(P)H ratio, and Ca(2+) uptake kinetics were not different in mitochondria from both groups. Together, these results suggest the existence of a substrate-specific regulation of the PTP in heart mitochondria and suggest that regular exercise results in a reduced sensitivity to Ca(2+)-induced PTP opening in presence of complex II substrates. 相似文献
175.
176.
177.
The role of the integral membrane nucleoporins Ndc1p and Pom152p in nuclear pore complex assembly and function 下载免费PDF全文
The nuclear pore complex (NPC) is a large channel that spans the two lipid bilayers of the nuclear envelope and mediates transport events between the cytoplasm and the nucleus. Only a few NPC components are transmembrane proteins, and the role of these proteins in NPC function and assembly remains poorly understood. We investigate the function of the three integral membrane nucleoporins, which are Ndc1p, Pom152p, and Pom34p, in NPC assembly and transport in Saccharomyces cerevisiae. We find that Ndc1p is important for the correct localization of nuclear transport cargoes and of components of the NPC. However, the role of Ndc1p in NPC assembly is partially redundant with Pom152p, as cells lacking both of these proteins show enhanced NPC disruption. Electron microscopy studies reveal that the absence of Ndc1p and Pom152p results in aberrant pores that have enlarged diameters and lack proteinaceous material, leading to an increased diffusion between the cytoplasm and the nucleus. 相似文献
178.
Maizel A 《Journal de la Société de Biologie》2006,200(3):221-227
179.
Dunne J Caron A Menu P Alayash AI Buehler PW Wilson MT Silaghi-Dumitrescu R Faivre B Cooper CE 《The Biochemical journal》2006,399(3):513-524
Haemoglobin initiates free radical chemistry. In particular, the interactions of peroxides with the ferric (met) species of haemoglobin generate two strong oxidants: ferryl iron and a protein-bound free radical. We have studied the endogenous defences to this reactive chemistry in a rabbit model following 20% exchange transfusion with cell-free haemoglobin stabilized in tetrameric form [via cross-linking with bis-(3,5-dibromosalicyl)fumarate]. The transfusate contained 95% oxyhaemoglobin, 5% methaemoglobin and 25 microM free iron. EPR spectroscopy revealed that the free iron in the transfusate was rendered redox inactive by rapid binding to transferrin. Methaemoglobin was reduced to oxyhaemoglobin by a slower process (t(1/2) = 1 h). No globin-bound free radicals were detected in the plasma. These redox defences could be fully attributed to a novel multifunctional role of plasma ascorbate in removing key precursors of oxidative damage. Ascorbate is able to effectively reduce plasma methaemoglobin, ferryl haemoglobin and globin radicals. The ascorbyl free radicals formed are efficiently re-reduced by the erythrocyte membrane-bound reductase (which itself uses intra-erythrocyte ascorbate as an electron donor). As well as relating to the toxicity of haemoglobin-based oxygen carriers, these findings have implications for situations where haem proteins exist outside the protective cell environment, e.g. haemolytic anaemias, subarachnoid haemorrhage, rhabdomyolysis. 相似文献
180.