全文获取类型
收费全文 | 1459篇 |
免费 | 71篇 |
国内免费 | 72篇 |
专业分类
1602篇 |
出版年
2023年 | 27篇 |
2022年 | 59篇 |
2021年 | 39篇 |
2020年 | 28篇 |
2019年 | 70篇 |
2018年 | 63篇 |
2017年 | 30篇 |
2016年 | 29篇 |
2015年 | 28篇 |
2014年 | 156篇 |
2013年 | 123篇 |
2012年 | 92篇 |
2011年 | 91篇 |
2010年 | 86篇 |
2009年 | 60篇 |
2008年 | 90篇 |
2007年 | 150篇 |
2006年 | 89篇 |
2005年 | 50篇 |
2004年 | 23篇 |
2003年 | 24篇 |
2002年 | 14篇 |
2001年 | 11篇 |
2000年 | 10篇 |
1999年 | 16篇 |
1998年 | 7篇 |
1997年 | 9篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 7篇 |
1983年 | 12篇 |
1982年 | 12篇 |
1981年 | 6篇 |
1980年 | 10篇 |
1979年 | 9篇 |
1978年 | 8篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1974年 | 7篇 |
1972年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有1602条查询结果,搜索用时 15 毫秒
991.
Avinash Mishra Prashant Singh Rana Aditya Mittal B. Jayaram 《Biochimica et Biophysica Acta - Proteins and Proteomics》2014,1844(10):1798-1807
Root-mean-square-deviation (RMSD), of computationally-derived protein structures from experimentally determined structures, is a critical index to assessing protein-structure-prediction-algorithms (PSPAs). The development of PSPAs to obtain 0 Å RMSD from native structures is considered central to computational biology. However, till date it has been quite challenging to measure how far a predicted protein structure is from its native — in the absence of a known experimental/native structure. In this work, we report the development of a metric “D2N” (distance to the native) — that predicts the “RMSD” of any structure without actually knowing the native structure. By combining physico-chemical properties and known universalities in spatial organization of soluble proteins to develop D2N, we demonstrate the ability to predict the distance of a proposed structure to within ± 1.5 ? error with a remarkable average accuracy of 93.6% for structures below 5 ? from the native. We believe that this work opens up a completely new avenue towards assigning reliable structures to whole proteomes even in the absence of experimentally determined native structures. The D2N tool is freely available at http://www.scfbio-iitd.res.in/software/d2n.jsp. 相似文献
992.
993.
Ariel Alcides Petruk Sonia Varriale Maria Rosaria Coscia Lelio Mazzarella Antonello Merlino Umberto Oreste 《生物化学与生物物理学报:生物膜》2013
Plasma membrane lipids significantly affect assembly and activity of many signaling networks. The present work is aimed at analyzing, by molecular dynamics simulations, the structure and dynamics of the CD3 ζζ dimer in palmitoyl-oleoyl-phosphatidylcholine bilayer (POPC) and in POPC/cholesterol/sphingomyelin bilayer, which resembles the raft membrane microdomain supposed to be the site of the signal transducing machinery. Both POPC and raft-like environment produce significant alterations in structure and flexibility of the CD3 ζζ with respect to nuclear magnetic resonance (NMR) model: the dimer is more compact, its secondary structure is slightly less ordered, the arrangement of the Asp6 pair, which is important for binding to the Arg residue in the alpha chain of the T cell receptor (TCR), is stabilized by water molecules. Different interactions of charged residues with lipids at the lipid–cytoplasm boundary occur when the two environments are compared. Furthermore, in contrast to what is observed in POPC, in the raft-like environment correlated motions between transmembrane and cytoplasmic regions are observed. Altogether the data suggest that when the TCR complex resides in the raft domains, the CD3 ζζ dimer assumes a specific conformation probably necessary to the correct signal transduction. 相似文献
994.
Kristin Scharnweber Matilda L. Andersson Fernando Chaguaceda Peter Eklv 《Ecology and evolution》2021,11(14):9804
- Stable isotopes represent a unique approach to provide insights into the ecology of organisms. δ13C and δ15N have specifically been used to obtain information on the trophic ecology and food‐web interactions. Trophic discrimination factors (TDF, Δ13C and Δ15N) describe the isotopic fractionation occurring from diet to consumer tissue, and these factors are critical for obtaining precise estimates within any application of δ13C and δ15N values. It is widely acknowledged that metabolism influences TDF, being responsible for different TDF between tissues of variable metabolic activity (e.g., liver vs. muscle tissue) or species body size (small vs. large). However, the connection between the variation of metabolism occurring within a single species during its ontogeny and TDF has rarely been considered.
- Here, we conducted a 9‐month feeding experiment to report Δ13C and Δ15N of muscle and liver tissues for several weight classes of Eurasian perch (Perca fluviatilis), a widespread teleost often studied using stable isotopes, but without established TDF for feeding on a natural diet. In addition, we assessed the relationship between the standard metabolic rate (SMR) and TDF by measuring the oxygen consumption of the individuals.
- Our results showed a significant negative relationship of SMR with Δ13C, and a significant positive relationship of SMR with Δ15N of muscle tissue, but not with TDF of liver tissue. SMR varies inversely with size, which translated into a significantly different TDF of muscle tissue between size classes.
- In summary, our results emphasize the role of metabolism in shaping‐specific TDF (i.e., Δ13C and Δ15N of muscle tissue) and especially highlight the substantial differences between individuals of different ontogenetic stages within a species. Our findings thus have direct implications for the use of stable isotope data and the applications of stable isotopes in food‐web studies.
995.
996.
Acierno JP Braden BC Klinke S Goldbaum FA Cauerhff A 《Journal of molecular biology》2007,374(1):130-146
The somatic mutations accumulated in variable and framework regions of antibodies produce structural changes that increase the affinity towards the antigen. This implies conformational and non covalent bonding changes at the paratope, as well as possible quaternary structure changes and rearrangements at the VH-VL interface. The consequences of the affinity maturation on the stability of the Fv domain were studied in a system composed of two closely related antibodies, F10.6.6 and D44.1, which recognize the same hen egg-white lysozyme (HEL) epitope. The mAb F10.6.6 has an affinity constant 700 times higher than D44.1, due to a higher surface complementarity to HEL. The structure of the free form of the Fab F10.6.6 presented here allows a comparative study of the conformational changes produced upon binding to antigen. By means of structural comparison, kinetics and thermodynamics of binding and stability studies on Fab and Fv fragments of both antibodies, we have determined that the affinity maturation process of anti-protein antibodies affects the shape of the combining site and the secondary structure content of the variable domain, stabilizes the VH-VL interaction, and consequently produces an increase of the Fv domain stability, improving the binding to antigen. 相似文献
997.
《Saudi Journal of Biological Sciences》2022,29(4):2573-2581
Porphyromonas gingivalis, the cause of periodontitis, is also linked to many systemic disorders due to its citrullination capability from a unique peptidyl arginine deiminase (PPAD). Protein citrullination is able to trigger an autoimmune response, increasing the severity of rheumatoid arthritis. The main objective of this study is to evaluate the inhibitory activity of Cratoxylym cochinchinense leaves extract towards the PPAD in vitro and in silico. Methanolic extract of Cratoxylum cochinchinense (CCM) was tested for total phenolic and flavonoid contents along with antioxidative assays. Inhibition of PPAD activities was conducted thereafter using recombinant PPAD in cell lysate. Phytocompounds postulated present in the CCM such as mangiferin, vismiaquinone A, δ-tocotrienol and α-tocotrienol and canophyllol were used as ligands in a simulated docking study against PPAD. Results obtained indicated high antioxidant potential in CCM while recording abundant phenolic (129.0 ± 2.5495 mg GA/g crude extract) and flavonoid (159.0 ± 2.1529 mg QE/g crude extract) contents. A dose-dependent inhibition of PPAD was observed when CCM was evaluated at various concentrations. CCM at 1 mg/mL exhibited citrulline concentration of 24.37 ± 3.25 mM which was 5 times lower than the negative control (114.23 ± 3.31 mM). Molecular docking simulation revealed that mangiferin and vismiaquinone A engaged in H-bonding and pi-pi interactions with important active site residues (Asp130, Arg152, Arg154 and Trp127) of PPAD and could be the potential phytochemicals that accounted for the inhibitory activities observed in the methanolic leaves extract. As such, CCM could be further explored for its therapeutic properties not only for periodontitis, but also for other systemic diseases like rheumatoid arthritis. 相似文献
998.
《Saudi Journal of Biological Sciences》2022,29(7):103312
The aim of this study is to assess the antioxidative profile and related pharmacological potentialities of the ethanolic extract of Amischotolype mollissima leaves, traditionally used in treating pain, injury, malarial fever, epilepsy and hyperacidity, followed by a computational approach for the analysis of bioactive compounds identified by GC–MS. In GC–MS analysis, the extract yielded ten compounds, with 4,6-di-t-butyl-2-alpha-methyl benzyl phenol having the highest amount. In vitro investigation of the antioxidative properties of the plant was conducted with 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical and hydrogen peroxide scavenging assays. The amounts of secondary metabolites phenolics, flavonoids, and tannins were measured at 142 mg GAE/g, 534 mg QE/g, and 110 mg GAE/g, respectively. An acute toxicity study was carried out on mice, which revealed no toxicity up to the dosage of 4000 mg/kg bw. For the dosages of extract at 250 and 500 mg/kg bw, the writhing response test induced by acetic acid exhibited a statistically significant (p < 0.05) analgesic effect in mice. The oral glucose tolerance test (OGTT) and alpha-glucosidase enzyme inhibitory activity assay were used to examine the antihyperglycemic potential, in which the extract reduced the blood glucose level to 6.22 mmol/l and 3.82 mmol/l, at dosages of 250 and 500 mg/kg bw, respectively at 60 min in OGTT even though no activity was observed in the α-glucosidase enzyme inhibitory assay. In an antibacterial assay, the extract's minimum inhibitory concentration (MIC) against E. coli, P. aeruginosa, and S. aureus was determined to be 8, 16, and 8 µg/ml, respectively. This study shows that the usage of A. mollissima leaves in folklore medication is justified. 相似文献
999.
《Molecular & cellular proteomics : MCP》2022,21(5):100212
Plasma is an important biofluid for clinical research and diagnostics. In the clinic, unpredictable delays—from minutes to hours—between blood collection and plasma generation are often unavoidable. These delays can potentially lead to protein degradation and modification and might considerably affect intact protein measurement methods such as sandwich enzyme-linked immunosorbent assays that bind proteins on two epitopes to increase specificity, thus requiring largely intact protein structures. Here, we investigated, using multiple reaction monitoring mass spectrometry (MRM-MS), how delays in plasma processing affect peptide-centric “bottom-up” proteomics. We used validated assays for proteotypic peptide surrogates of 270 human proteins to analyze plasma generated after whole blood had been kept at room temperature from 0 to 40 h to mimic delays that occur in the clinic. Moreover, we evaluated the impact of different plasma-thawing conditions on MRM-based plasma protein quantitation. We demonstrate that >90% of protein concentration measurements were unaffected by the thawing procedure and by up to 40-h delayed plasma generation, reflected by relative standard deviations (RSDs) of <30%. Of the 159 MRM assays that yielded quantitative results in 60% of the measured time points, 139 enabled a stable protein quantitation (RSD <20%), 14 showed a slight variation (RSD 20–30%), and 6 appeared unstable/irreproducible (RSD > 30%). These results demonstrate the high robustness and thus the potential for MRM-based plasma-protein quantitation to be used in a clinical setting. In contrast to enzyme-linked immunosorbent assay, peptide-based MRM assays do not require intact three-dimensional protein structures for an accurate and precise quantitation of protein concentrations in the original sample. 相似文献
1000.
为破解东北经济社会发展受水资源承载力刚性约束的迷局,以典型老工业基地辽宁本溪市为例,通过产业结构区位熵明确本溪市各产业在全国的发展水平,采用灰色关联度、结构协调度分析产业结构和用水结构的相关程度和协调程度,并通过结构偏差系数对各产业间和行业间的协调程度进行对比分析。结果表明:从2008-2017年,本溪市一产发展稳定,二产在经历过大幅下跌之后缓慢增长,三产在2016年之后成为本溪市的支柱产业;三大产业比例由2008年的0.06 ∶ 0.60 ∶ 0.34调整为2017年的0.06 ∶ 0.44 ∶ 0.50,曾经占主导优势的重工业及化工业都呈现下降趋势,产业结构发生转变。三大产业平均用水量比例由2008年的0.39 ∶ 0.59 ∶ 0.02 调整为2017年的0.41 ∶ 0.51 ∶ 0.07,总用水量减少了1/4以上;规模以上行业中,大部分行业的用水量随着产值的增加而增加,需要进一步转换生产工艺;产值最高的黑色金属冶炼和压延加工业从水资源高效利用角度可作为大力扶持发展的产业。行业生产规模比较大的黑色金属矿采选业、医药制造业、非金属矿物制品业和黑色金属冶炼和压延加工业等产业与用水的结构逐渐朝着均衡的状态发展,仍需要一定时间才能达到协调。 相似文献