全文获取类型
收费全文 | 431篇 |
免费 | 14篇 |
专业分类
445篇 |
出版年
2023年 | 3篇 |
2022年 | 4篇 |
2021年 | 16篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2018年 | 7篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 15篇 |
2014年 | 15篇 |
2013年 | 30篇 |
2012年 | 14篇 |
2011年 | 14篇 |
2010年 | 5篇 |
2009年 | 18篇 |
2008年 | 25篇 |
2007年 | 27篇 |
2006年 | 13篇 |
2005年 | 12篇 |
2004年 | 16篇 |
2003年 | 8篇 |
2002年 | 8篇 |
2001年 | 9篇 |
2000年 | 3篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 10篇 |
1991年 | 9篇 |
1990年 | 10篇 |
1989年 | 4篇 |
1988年 | 11篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 9篇 |
1978年 | 7篇 |
1977年 | 3篇 |
1976年 | 5篇 |
1974年 | 10篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1971年 | 2篇 |
排序方式: 共有445条查询结果,搜索用时 15 毫秒
51.
Niehuis O Hartig G Grath S Pohl H Lehmann J Tafer H Donath A Krauss V Eisenhardt C Hertel J Petersen M Mayer C Meusemann K Peters RS Stadler PF Beutel RG Bornberg-Bauer E McKenna DD Misof B 《Current biology : CB》2012,22(14):1309-1313
The phylogeny of insects, one of the most spectacular radiations of life on earth, has received considerable attention. However, the evolutionary roots of one intriguing group of insects, the twisted-wing parasites (Strepsiptera), remain unclear despite centuries of study and debate. Strepsiptera exhibit exceptional larval developmental features, consistent with a predicted step from direct (hemimetabolous) larval development to complete metamorphosis that could have set the stage for the spectacular radiation of metamorphic (holometabolous) insects. Here we report the sequencing of a Strepsiptera genome and show that the analysis of sequence-based genomic data (comprising more than 18 million nucleotides from nearly 4,500 genes obtained from a total of 13 insect genomes), along with genomic metacharacters, clarifies the phylogenetic origin of Strepsiptera and sheds light on the evolution of holometabolous insect development. Our results provide overwhelming support for Strepsiptera as the closest living relatives of beetles (Coleoptera). They demonstrate that the larval developmental features of Strepsiptera, reminiscent of those of hemimetabolous insects, are the result of convergence. Our analyses solve the long-standing enigma of the evolutionary roots of Strepsiptera and reveal that the holometabolous mode of insect development is more malleable than previously thought. 相似文献
52.
The physicochemical properties of cellular environments with a high macromolecular content have been systematically characterized to explain differences observed in the diffusion coefficients, kinetics parameters, and thermodynamic properties of proteins inside and outside of cells. However, much less attention has been given to the effects of macromolecular crowding on cell physiology. Here, we review recent findings that shed some light on the role of crowding in various cellular processes, such as reduction of biochemical activities, structural reorganization of the cytoplasm, cytoplasm fluidity, and cellular dormancy. We conclude by presenting some unresolved problems that require the attention of biophysicists, biochemists, and cell physiologists. Although it is still underappreciated, macromolecular crowding plays a critical role in life as we know it. 相似文献
53.
The bioterror threat of a smallpox outbreak in an unvaccinated population has mobilized efforts to develop new antipoxviral agents. By screening a library of known drugs, we identified 13 compounds that inhibited vaccinia virus replication at noncytotoxic doses. The anticancer drug mitoxantrone is unique among the inhibitors identified in that it has no apparent impact on viral gene expression. Rather, it blocks processing of viral structural proteins and assembly of mature progeny virions. The isolation of mitoxantrone-resistant vaccinia strains underscores that a viral protein is the likely target of the drug. Whole-genome sequencing of mitoxantrone-resistant viruses pinpointed missense mutations in the N-terminal domain of vaccinia DNA ligase. Despite its favorable activity in cell culture, mitoxantrone administered intraperitoneally at the maximum tolerated dose failed to protect mice against a lethal intranasal infection with vaccinia virus. 相似文献
54.
Antczak C Shum D Escobar S Bassit B Kim E Seshan VE Wu N Yang G Ouerfelli O Li YM Scheinberg DA Djaballah H 《Journal of biomolecular screening》2007,12(4):521-535
The human mitochondrial peptide deformylase (HsPDF) provides a potential new target for broadly acting antiproliferative agents. To identify novel nonpeptidomimetic and nonhydroxamic acid-based inhibitors of HsPDF, the authors have developed a high-throughput screening (HTS) strategy using a fluorescence polarization (FP)-based binding assay as the primary assay for screening chemical libraries, followed by an enzymatic-based assay to confirm hits, prior to characterization of their antiproliferative activity against established tumor cell lines. The authors present the results and performance of the established strategy tested in a pilot screen of 2880 compounds and the identification of the 1st inhibitors. Two common scaffolds were identified within the hits. Furthermore, cytotoxicity studies revealed that most of the confirmed hits have antiproliferative activity. These findings demonstrate that the designed strategy can identify novel functional inhibitors and provide a powerful alternative to the use of functional assays in HTS and support the hypothesis that HsPDF inhibitors may constitute a new class of antiproliferative agent. 相似文献
55.
Maraldi T Prata C Fiorentini D Zambonin L Landi L Hakim G 《Free radical research》2007,41(12):1348-1357
In M07e cells, a human megakaryocytic leukaemia line, reactive oxygen species (ROS) are generated in response to cytokines acting as intracellular messengers to modulate glucose transport. The aim of this work was to study the signal cascade involved in the acute glucose transport activation in cells exposed to growth factors, such as granulocyte macrophage-colony stimulation factor (GM-CSF) and thrombopoietin (TPO), to better understand some aspects of the aberrant proliferation in leukaemia. Results confirm ROS involvement in modulation of glucose transport in this cell line. Furthermore, GM-CSF and TPO produced changes in Glut1 phosphorylation and specific inhibitors employed to identify protein kinases involved in Glut activation by these cytokines proved that Akt, PLCγ, Syk and the Src family take part in signal transduction leading to Glut1 activation. 相似文献
56.
Ramajayam R Giridhar R Yadav MR Djaballah H Shum D Radu C 《Journal of enzyme inhibition and medicinal chemistry》2007,22(6):716-721
Novel substituted 5,7-diaryl-2,3-dihydro-1,4-diazepines and 4,6-diaryl-2-aminopyrimidines were synthesized and tested for their antiproliferative activity. Title compounds were obtained by cyclocondensation of a substituted flavone with ethylenediamine and guanidine respectively. The cytotoxicity in vitro against various human leukemic cancer cell lines viz., Jurkat, HL60, MOLT3, NCEB-1, K562 was determined. 相似文献
57.
Soudani N Ben Amara I Troudi A Hakim A Bouaziz H Ayadi Makni F Zeghal KM Zeghal N 《Journal of physiology and biochemistry》2011,67(4):577-588
Excess chromium (Cr) exposure is associated with various pathological conditions including hematological dysfunction. The
generation of oxidative stress is one of the plausible mechanisms behind Cr-induced cellular deteriorations. The efficacy
of selenium (Se) to combat Cr-induced oxidative damage in the erythrocytes of adult rats was investigated in the current study.
Female Wistar rats were randomly divided into four groups of six each: group I served as controls which received standard
diet, group II received in drinking water K2Cr2O7 alone (700 ppm), group III received both K2Cr2O7 and Se (0.5 Na2SeO3 mg/kg of diet), and group IV received Se (0.5 mg/kg of diet) for 3 weeks. Rats exposed to K2Cr2O7 showed an increase of malondialdehyde and protein carbonyl levels and a decrease of sulfhydryl content, glutathione, non-protein
thiol, and vitamin C levels. A decrease of enzyme activities like catalase, glutathione peroxidase, and superoxide dismutase
activities was also noted. Co-administration of Se with K2Cr2O7 restored the parameters cited above to near-normal values. Therefore, our investigation revealed that Se was a useful element
preventing K2Cr2O7-induced erythrocyte damages. 相似文献
58.
Neelapu SS Kwak LW Kobrin CB Reynolds CW Janik JE Dunleavy K White T Harvey L Pennington R Stetler-Stevenson M Jaffe ES Steinberg SM Gress R Hakim F Wilson WH 《Nature medicine》2005,11(9):986-991
The role of B cells in T-cell priming is unclear, and the effects of B-cell depletion on immune responses to cancer vaccines are unknown. Although results from some mouse models suggest that B cells may inhibit induction of T cell-dependent immunity by competing with antigen-presenting cells for antigens, skewing T helper response toward a T helper 2 profile and/or inducing T-cell tolerance, results from others suggest that B cells are necessary for priming as well as generation of T-cell memory. We assessed immune responses to a well-characterized idiotype vaccine in individuals with severe B-cell depletion but normal T cells after CD20-specific antibody-based chemotherapy of mantle cell lymphoma in first remission. Humoral antigen- and tumor-specific responses were detectable but delayed, and they correlated with peripheral blood B-cell recovery. In contrast, vigorous CD4(+) and CD8(+) antitumor type I T-cell cytokine responses were induced in most individuals in the absence of circulating B cells. Analysis of relapsing tumors showed no mutations or change in expression of target antigen to explain escape from therapy. These results show that severe B-cell depletion does not impair T-cell priming in humans. Based on these results, it is justifiable to administer vaccines in the setting of B-cell depletion; however, vaccine boosts after B-cell recovery may be necessary for optimal humoral responses. 相似文献
59.
60.
Diana M. Gibb Hilda Kizito Elizabeth C. Russell Ennie Chidziva Eva Zalwango Ruth Nalumenya Moira Spyer Dinah Tumukunde Kusum Nathoo Paula Munderi Hope Kyomugisha James Hakim Heiner Grosskurth Charles F. Gilks A. Sarah Walker Phillipa Musoke 《PLoS medicine》2012,9(5)