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31.
Jessica L. Graham Carolyn M. Bauer Britt J. Heidinger Ellen D. Ketterson Timothy J. Greives 《Molecular ecology》2019,28(1):114-126
Annual reproductive success is often highest in individuals that initiate breeding early, yet relatively few individuals start breeding during this apparently optimal time. This suggests that individuals, particularly females who ultimately dictate when offspring are born, incur costs by initiating reproduction early in the season. We hypothesized that increases in the ageing rate of somatic cells may be one such cost. Telomeres, the repetitive DNA sequences on the ends of chromosomes, may be good proxies of biological wear and tear as they shorten with age and in response to stress. Using historical data from a long‐term study population of dark‐eyed juncos (Junco hyemalis), we found that telomere loss between years was greater in earlier breeding females, regardless of chronological age. There was no relationship between telomere loss and the annual number of eggs laid or chicks that reached independence. However, telomere loss was greater when temperatures were cooler, and cooler temperatures generally occur early in the season. This suggests that environmental conditions could be the primary cause of accelerated telomere loss in early breeders. 相似文献
32.
Britt Paulsen Kim Alex Fredriksen Dirk Petersen Louis Maes An Matheeussen Ali-Oddin Naemi Anne Aamdal Scheie Roger Simm Rui Ma Baojie Wan Scott Franzblau Lise-Lotte Gundersen 《Bioorganic & medicinal chemistry》2019,27(4):620-629
(+)-N6-Hydroxyagelasine D, the enantiomer of the proposed structure of (?)-ageloxime D, as well as N6-hydroxyagelasine analogs were synthesized by selective N-7 alkylation of N6-[tert-butyl(dimethyl)silyloxy]-9-methyl-9H-purin-6-amine in order to install the terpenoid side chain, followed by fluoride mediated removal of the TBDMS-protecting group. N6-Hydroxyagelasine D and the analog carrying a geranylgeranyl side chain displayed profound antimicrobial activities against several pathogenic bacteria and protozoa and inhibited bacterial biofilm formation. However these compounds were also toxic towards mammalian fibroblast cells (MRC-5). The spectral data of N6-hydroxyagelasine D did not match those reported for ageloxime D before. Hence, a revised structure of ageloxime D was proposed. Basic hydrolysis of agelasine D gave (+)-N-[4-amino-6-(methylamino)pyrimidin-5-yl]-N-copalylformamide, a compound with spectral data in full agreement with those reported for (?)-ageloxime D. 相似文献
33.
Therese S. Høiem Maria K. Andersen Marta Martin-Lorenzo Rémi Longuespée Britt S.R. Claes Anna Nordborg Frédéric Dewez Benjamin Balluff Marco Giampà Animesh Sharma Lars Hagen Ron M.A. Heeren Tone F. Bathen Guro F. Giskeødegård Sebastian Krossa May-Britt Tessem 《Proteomics》2022,22(10):2100223
MALDI MS imaging (MSI) is a powerful analytical tool for spatial peptide detection in heterogeneous tissues. Proper sample preparation is crucial to achieve high quality, reproducible measurements. Here we developed an optimized protocol for spatially resolved proteolytic peptide detection with MALDI time-of-flight MSI of fresh frozen prostate tissue sections. The parameters tested included four different tissue washes, four methods of protein denaturation, four methods of trypsin digestion (different trypsin densities, sprayers, and incubation times), and five matrix deposition methods (different sprayers, settings, and matrix concentrations). Evaluation criteria were the number of detected and excluded peaks, percentage of high mass peaks, signal-to-noise ratio, spatial localization, and average intensities of identified peptides, all of which were integrated into a weighted quality evaluation scoring system. Based on these scores, the optimized protocol included an ice-cold EtOH+H2O wash, a 5 min heating step at 95°C, tryptic digestion incubated for 17h at 37°C and CHCA matrix deposited at a final amount of 1.8 μg/mm2. Including a heat-induced protein denaturation step after tissue wash is a new methodological approach that could be useful also for other tissue types. This optimized protocol for spatial peptide detection using MALDI MSI facilitates future biomarker discovery in prostate cancer and may be useful in studies of other tissue types. 相似文献
34.
Electron paramagnetic resonance (EPR) spectroscopy has often played a crucial role in characterizing the various cofactors and processes of photosynthesis, and photosystem II and its oxygen evolving chemistry is no exception. Until recently, the application of EPR spectroscopy to the characterization of the oxygen evolving complex (OEC) has been limited to the S2-state of the Kok cycle. However, in the past few years, continuous wave-EPR signals have been obtained for both the S0- and S1-state as well as for the S2 (radical)(Z)-state of a number of inhibited systems. Furthermore, the pulsed EPR technique of electron spin echo electron nuclear double resonance spectroscopy has been used to directly probe the 55Mn nuclei of the manganese cluster. In this review, we discuss how the EPR data obtained from each of these states of the OEC Kok cycle are being used to provide insight into the physical and electronic structure of the manganese cluster and its interaction with the key tyrosine, Y(Z). 相似文献
35.
Perni RB Pitlik J Britt SD Court JJ Courtney LF Deininger DD Farmer LJ Gates CA Harbeson SL Levin RB Lin C Lin K Moon YC Luong YP O'Malley ET Rao BG Thomson JA Tung RD Van Drie JH Wei Y 《Bioorganic & medicinal chemistry letters》2004,14(6):1441-1446
The alpha-ketoamide warhead (e.g., 15) was found to be a practical replacement for aliphatic aldehydes in a series of HCV NS3.4A protease inhibitors. Structure-activity relationships and prime side optimization are discussed. 相似文献
36.
Britt BM 《Journal of biochemistry and molecular biology》2004,37(4):394-401
The purpose of this paper is to suggest that the prominence of Haldane's explanation for enzyme catalysis significantly hinders investigations in understanding enzyme structure and function. This occurs despite the existence of much evidence that the Haldane model cannot embrace. Some of the evidence, in fact, disproves the model. A brief history of the explanation of enzyme catalysis is presented. The currently accepted view of enzyme catalysis--the Haldane model--is examined in terms of its strengths and weaknesses. An alternate model for general enzyme catalysis (the Shifting Specificity model) is reintroduced and an assessment of why it may be superior to the Haldane model is presented. Finally, it is proposed that a re-examination of many current aspects in enzyme structure and function (specifically, protein folding, x-ray and NMR structure analyses, enzyme stability curves, enzyme mimics, catalytic antibodies, and the loose packing of enzyme folded forms) in terms of the new model may offer crucial insights. 相似文献
37.
38.
Donor APCs are required for maximal GVHD but not for GVL 总被引:23,自引:0,他引:23
Matte CC Liu J Cormier J Anderson BE Athanasiadis I Jain D McNiff J Shlomchik WD 《Nature medicine》2004,10(9):987-992
Graft-versus-host disease (GVHD) is a major source of morbidity in allogenic stem cell transplantation. We previously showed that recipient antigen-presenting cells (APCs) are required for CD8-dependent GVHD in a mouse model across only minor histocompatibility antigens (minor H antigens). However, these studies did not address the function of donor-derived APCs after GVHD is initiated. Here we show that GVHD develops in recipients of donor major histocompatibility complex class I-deficient (MHC I(-)) bone marrow. Thus, after initial priming, CD8 cells caused GVHD without a further requirement for hematopoietic APCs, indicating that host APCs are necessary and sufficient for GHVD. Nonetheless, GVHD was less severe in recipients of MHC I(-) bone marrow. Therefore, once initiated, GVHD is intensified by donor-derived cells, most probably donor APCs cross-priming alloreactive CD8 cells. Nevertheless, donor APCs were not required for CD8-mediated graft-versus-leukemia (GVL) against a mouse model of chronic-phase chronic myelogenous leukemia. These studies identify donor APCs as a new target for treating GVHD, which may preserve GVL. 相似文献
39.
Envelopment of human cytomegalovirus occurs by budding into Golgi-derived vacuole compartments positive for gB,Rab 3, trans-golgi network 46, and mannosidase II
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Although considerable progress has been made towards characterizing virus assembly processes, assignment of the site of tegumentation and envelopment for human cytomegalovirus (HCMV) is still not clear. In this study, we examined the envelopment of HCMV particles in human lung fibroblasts (HF) HL 411 and HL 19, human umbilical vein endothelial cells, human pulmonary arterial endothelial cells, and arterial smooth muscle cells at different time points after infection by electron microscopy (EM), immunohistochemistry, and confocal microscopy analysis. Double-immunofluorescence labeling experiments demonstrated colocalization of the HCMV glycoprotein B (gB) with the Golgi resident enzyme mannosidase II, the Golgi marker TGN (trans-Golgi network) 46, and the secretory vacuole marker Rab 3 in all cell types investigated. Final envelopment of tegumented capsids was observed at 5 days postinfection by EM, when tegumented capsids budded into subcellular compartments located in the cytoplasm, in close proximity to the Golgi apparatus. Immunogold labeling and EM analysis confirmed staining of the budding compartment with HCMV gB, Rab 3, and mannosidase II in HL 411 cells. However, the markers Rab 1, Rab 2, Rab 7, Lamp 1 (late endosomes and lysosomes), and Lamp 2 (lysosomes) neither showed specific staining of the budding compartment in the immunogold labeling experiments nor colocalized with gB in the immunofluorescent colocalization experiments in any cell type studied. Together, these results suggest that the final envelopment of HCMV particles takes place mainly into a Golgi-derived secretory vacuole destined for the plasma membrane, which may release new infectious virus particles by fusion with the plasma membrane. 相似文献
40.
Certain phenolic compounds represent a distinct class of Photosystem (PS) II QB site inhibitors. In this paper, we report a detailed study of the effects of 2,4,6-trinitrophenol (TNP) and other phenolic inhibitors, bromoxynil and dinoseb, on PS II energetics. In intact PS II, phenolic inhibitors bound to only 90-95% of QB sites even at saturating concentrations. The remaining PS II reaction centers (5-10%) showed modified QA to QB electron transfer but were sensitive to urea/triazine inhibitors. The binding of phenolic inhibitors was 30- to 300-fold slower than the urea/triazine class of QB site inhibitors, DCMU and atrazine. In the sensitive centers, the S2QA− state was 10-fold less stable in the presence of phenolic inhibitors than the urea/triazine herbicides. In addition, the binding affinity of phenolic herbicides was decreased 10-fold in the S2QA− state than the S1QA state. However, removal of the oxygen-evolving complex (OEC) and associated extrinsic polypeptides by hydroxylamine (HA) washing abolished the slow binding kinetics as well as the destabilizing effects on the charge-separated state. The S2-multiline electron paramagnetic resonance (EPR) signal and the ‘split’ EPR signal, originating from the S2YZ state showed no significant changes upon binding of phenolic inhibitors at the QB site. We thus propose a working model where QA redox potential is lowered by short-range conformational changes induced by phenolic inhibitor binding at the QB niche. Long-range effects of HA-washing eliminate this interaction, possibly by allowing more flexibility in the QB site. 相似文献