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111.
MG132 Induces Expression of Monocyte Chemotactic Protein‐Induced Protein 1 in Vascular Smooth Muscle Cells 下载免费PDF全文
112.
Alon N Dao P Hajirasouliha I Hormozdiari F Sahinalp SC 《Bioinformatics (Oxford, England)》2008,24(13):i241-i249
Protein-protein interaction (PPI) networks of many organisms share global topological features such as degree distribution, k-hop reachability, betweenness and closeness. Yet, some of these networks can differ significantly from the others in terms of local structures: e.g. the number of specific network motifs can vary significantly among PPI networks. Counting the number of network motifs provides a major challenge to compare biomolecular networks. Recently developed algorithms have been able to count the number of induced occurrences of subgraphs with k < or = 7 vertices. Yet no practical algorithm exists for counting non-induced occurrences, or counting subgraphs with k > or = 8 vertices. Counting non-induced occurrences of network motifs is not only challenging but also quite desirable as available PPI networks include several false interactions and miss many others. In this article, we show how to apply the 'color coding' technique for counting non-induced occurrences of subgraph topologies in the form of trees and bounded treewidth subgraphs. Our algorithm can count all occurrences of motif G' with k vertices in a network G with n vertices in time polynomial with n, provided k = O(log n). We use our algorithm to obtain 'treelet' distributions for k < or = 10 of available PPI networks of unicellular organisms (Saccharomyces cerevisiae Escherichia coli and Helicobacter Pyloris), which are all quite similar, and a multicellular organism (Caenorhabditis elegans) which is significantly different. Furthermore, the treelet distribution of the unicellular organisms are similar to that obtained by the 'duplication model' but are quite different from that of the 'preferential attachment model'. The treelet distribution is robust w.r.t. sparsification with bait/edge coverage of 70% but differences can be observed when bait/edge coverage drops to 50%. 相似文献
113.
Tegley CM Viswanadhan VN Biswas K Frohn MJ Peterkin TA Chang C Bürli RW Dao JH Veith H Rogers N Yoder SC Biddlecome G Tagari P Allen JR Hungate RW 《Bioorganic & medicinal chemistry letters》2008,18(14):3925-3928
Inhibition of the PHD2 enzyme has been associated with increased red blood cell levels. From a screening hit, a series of novel hydroxyl-thiazoles were developed as potent PHD2 inhibitors. 相似文献
114.
Thi Thanh Hien Dao Roberto Chacon Puig Hye Kyong Kim Cornelis Erkelens Alfons W.M. Lefeber Huub J.M. Linthorst Young Hae Choi Robert Verpoorte 《Plant Physiology and Biochemistry》2009,47(2):146-152
Benzothiadiazole (BTH) is a functional analog of the plant endogenous hormone-like compound, salicylic acid (SA), which is required for the induction of plant defense genes leading to systemic acquired resistance (SAR). Previous molecular and genetic studies have suggested that BTH itself might potentiate SAR resulting in the induction of several pathogenesis-related (PR) genes. However, the changes in the metabolome, which occur as a result of BTH-treatment, remain unclear. In this study, metabolic alterations in BTH-treated Arabidopsis thaliana were investigated using nuclear magnetic resonance (NMR) spectroscopy followed by multivariate data analyses such as principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA). Both PCA and PLS-DA show that increase of glucose, glutamine, inositol, malic acid, sucrose, and threonine as well as BTH and its degraded metabolites contribute to the clear discrimination of the metabolome of BTH-treated Arabidopsis from control plants. However, the levels of phenolic metabolites, which have generally been observed to be induced by other signaling molecules were significantly reduced in BTH-treated Arabidopsis. In addition to these changes due to BTH-treatment, it was also found that the EtOH used as a solvent in this treatment may per se act as an inducer of the accumulation of a flavonoid. 相似文献
115.
Dao VT Dowd MK Gaspard C Martin MT Hémez J Laprévote O Mayer M Michelot RJ 《Bioorganic & medicinal chemistry》2003,11(9):2001-2006
New dithiane or dithiolane derivatives of gossypol and gossypolone were synthesized with dithiolethane or dithiolpropane in the presence of BF(3)/Et(2)O. These thioderivatives exhibited low toxicity on KB cells (human epidermoid carcinoma cells of the mouth). They react easily with electrophiles in aprotic solvents to regenerate gossypolone or to form dehydrogossypoldithianes and dehydrogossypoldithiolanes, which display higher toxicity on KB cells. In addition, the low toxicity of gossypol thioderivatives was reversed by nitric oxide donors in physiological media. These experiments suggest that gossypol and gossypolone dithianes and dithiolanes can be used as prodrugs that target tumor cells surrounded by high concentrations of nitric oxide. 相似文献
116.
Chandramohanadas R Park Y Lui L Li A Quinn D Liew K Diez-Silva M Sung Y Dao M Lim CT Preiser PR Suresh S 《PloS one》2011,6(6):e20869
Upon infection and development within human erythrocytes, P. falciparum induces alterations to the infected RBC morphology and bio-mechanical properties to eventually rupture the host cells through parasitic and host derived proteases of cysteine and serine families. We used previously reported broad-spectrum inhibitors (E64d, EGTA-AM and chymostatin) to inhibit these proteases and impede rupture to analyze mechanical signatures associated with parasite escape. Treatment of late-stage iRBCs with E64d and EGTA-AM prevented rupture, resulted in no major RBC cytoskeletal reconfiguration but altered schizont morphology followed by dramatic re-distribution of three-dimensional refractive index (3D-RI) within the iRBC. These phenotypes demonstrated several-fold increased iRBC membrane flickering. In contrast, chymostatin treatment showed no 3D-RI changes and caused elevated fluctuations solely within the parasitophorous vacuole. We show that E64d and EGTA-AM supported PV breakdown and the resulting elevated fluctuations followed non-Gaussian pattern that resulted from direct merozoite impingement against the iRBC membrane. Optical trapping experiments highlighted reduced deformability of the iRBC membranes upon rupture-arrest, more specifically in the treatments that facilitated PV breakdown. Taken together, our experiments provide novel mechanistic interpretations on the role of parasitophorous vacuole in maintaining the spherical schizont morphology, the impact of PV breakdown on iRBC membrane fluctuations leading to eventual parasite escape and the evolution of membrane stiffness properties of host cells in which merozoites were irreversibly trapped, recourse to protease inhibitors. These findings provide a comprehensive, previously unavailable, body of information on the combined effects of biochemical and biophysical factors on parasite egress from iRBCs. 相似文献
117.
Cherkasov A Hsing M Zoraghi R Foster LJ See RH Stoynov N Jiang J Kaur S Lian T Jackson L Gong H Swayze R Amandoron E Hormozdiari F Dao P Sahinalp C Santos-Filho O Axerio-Cilies P Byler K McMaster WR Brunham RC Finlay BB Reiner NE 《Journal of proteome research》2011,10(3):1139-1150
Mortality attributable to infection with methicillin-resistant Staphylococcus aureus (MRSA) has now overtaken the death rate for AIDS in the United States, and advances in research are urgently needed to address this challenge. We report the results of the systematic identification of protein-protein interactions for the hospital-acquired strain MRSA-252. Using a high-throughput pull-down strategy combined with quantitative proteomics to distinguish specific from nonspecific interactors, we identified 13,219 interactions involving 608 MRSA proteins. Consecutive analyses revealed that this protein interaction network (PIN) exhibits scale-free organization with the characteristic presence of highly connected hub proteins. When clinical and experimental antimicrobial targets were queried in the network, they were generally found to occupy peripheral positions in the PIN with relatively few interacting partners. In contrast, the hub proteins identified in this MRSA PIN that are essential for network integrity and stability have largely been overlooked as drug targets. Thus, this empirical MRSA-252 PIN provides a rich source for identifying critical proteins essential for network stability, many of which can be considered as prospective antimicrobial drug targets. 相似文献
118.
Subacute calorie restriction and rapamycin discordantly alter mouse liver proteome homeostasis and reverse aging effects 下载免费PDF全文
Dao‐Fu Dai Ying A. Chiao Ellen K. Quarles Edward J. Hsieh David Crispin Jason H. Bielas Nolan G. Ericson Richard P. Beyer Vivian L. MacKay Michael J. MacCoss Peter S. Rabinovitch 《Aging cell》2015,14(4):547-557
Calorie restriction (CR) and rapamycin (RP) extend lifespan and improve health across model organisms. Both treatments inhibit mammalian target of rapamycin (mTOR) signaling, a conserved longevity pathway and a key regulator of protein homeostasis, yet their effects on proteome homeostasis are relatively unknown. To comprehensively study the effects of aging, CR, and RP on protein homeostasis, we performed the first simultaneous measurement of mRNA translation, protein turnover, and abundance in livers of young (3 month) and old (25 month) mice subjected to 10‐week RP or 40% CR. Protein abundance and turnover were measured in vivo using 2H3–leucine heavy isotope labeling followed by LC‐MS/MS, and translation was assessed by polysome profiling. We observed 35–60% increased protein half‐lives after CR and 15% increased half‐lives after RP compared to age‐matched controls. Surprisingly, the effects of RP and CR on protein turnover and abundance differed greatly between canonical pathways, with opposite effects in mitochondrial (mt) dysfunction and eIF2 signaling pathways. CR most closely recapitulated the young phenotype in the top pathways. Polysome profiles indicated that CR reduced polysome loading while RP increased polysome loading in young and old mice, suggesting distinct mechanisms of reduced protein synthesis. CR and RP both attenuated protein oxidative damage. Our findings collectively suggest that CR and RP extend lifespan in part through the reduction of protein synthetic burden and damage and a concomitant increase in protein quality. However, these results challenge the notion that RP is a faithful CR mimetic and highlight mechanistic differences between the two interventions. 相似文献
119.
基因工程菌大肠杆菌JM109富集废水中镍离子的研究 总被引:4,自引:2,他引:4
利用通过基因工程技术所构建的在细胞内同时表达出高特异性镍转运蛋白和金属硫蛋白的基因工程菌富集水体中的镍离子。菌体细胞对Ni2+的富集速率很快,富集过程满足Langmuir等温线模型。与原始宿主菌相比,经基因改造的基因工程菌不仅最大镍富集容量增加了5倍多,而且对pH值、离子强度的变化及其它共存重金属离子的影响都呈现出更强的适应性。相比而言,Na+、Ca2+、Cd2+、Pb2+的影响较小,但Mg2+、Hg2+和Cu2+所引起的负面效应较大。进一步的实验表明基因工程菌对Ni2+的富集行为不需要外加营养物质。 相似文献
120.
Clark RL Carter KC Mullen AB Coxon GD Owusu-Dapaah G McFarlane E Duong Thi MD Grant MH Tettey JN Mackay SP 《Bioorganic & medicinal chemistry letters》2007,17(3):624-627
The continual increase in drug resistance; the lack of new chemotherapeutic agents; the toxicity of existing agents and the increasing morbidity with HIV co-infection mean the search for new antileishmanial agents has never been more urgent. We have identified the benzodiazepines as a structural class for antileishmanial hit optimisation, and demonstrated that their in vitro activity is comparable with the clinically used drug, sodium stibogluconate, and that the compounds are not toxic to macrophages. 相似文献