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81.
Gordon J. Hildick-Smith Jeffrey D. Cooney Caterina Garone Laura S. Kremer Tobias B. Haack Jonathan N. Thon Non Miyata Daniel S. Lieber Sarah E. Calvo H. Orhan Akman Yvette Y. Yien Nicholas C. Huston Diana S. Branco Dhvanit I. Shah Matthew L. Freedman Carla M. Koehler Joseph E. Italiano Jr. Andreas Merkenschlager Skadi Beblo Tim M. Strom Thomas Meitinger Peter Freisinger M. Alice Donati Holger Prokisch Vamsi K. Mootha Salvatore DiMauro Barry H. Paw 《American journal of human genetics》2013
82.
Gordon?J. Hildick-Smith Jeffrey?D. Cooney Caterina Garone Laura?S. Kremer Tobias?B. Haack Jonathan?N. Thon Non Miyata Daniel?S. Lieber Sarah?E. Calvo H.?Orhan Akman Yvette?Y. Yien Nicholas?C. Huston Diana?S. Branco Dhvanit?I. Shah Matthew?L. Freedman Carla?M. Koehler Joseph?E. Italiano Jr. Andreas Merkenschlager Skadi Beblo Tim?M. Strom Thomas Meitinger Peter Freisinger M.?Alice Donati Holger Prokisch Vamsi?K. Mootha Salvatore DiMauro Barry?H. Paw 《American journal of human genetics》2013,93(5):906-914
We used exome sequencing to identify mutations in sideroflexin 4 (SFXN4) in two children with mitochondrial disease (the more severe case also presented with macrocytic anemia). SFXN4 is an uncharacterized mitochondrial protein that localizes to the mitochondrial inner membrane. sfxn4 knockdown in zebrafish recapitulated the mitochondrial respiratory defect observed in both individuals and the macrocytic anemia with megaloblastic features of the more severe case. In vitro and in vivo complementation studies with fibroblasts from the affected individuals and zebrafish demonstrated the requirement of SFXN4 for mitochondrial respiratory homeostasis and erythropoiesis. Our findings establish mutations in SFXN4 as a cause of mitochondriopathy and macrocytic anemia. 相似文献
83.
Müller CP Pum ME Amato D Schüttler J Huston JP Silva MA 《Journal of neurochemistry》2011,119(3):419-446
Anesthesia describes a complex state composed of immobility, amnesia, hypnosis (sleep or loss of consciousness), analgesia, and muscle relaxation. Bottom-up approaches explain anesthesia by an interaction of the anesthetic with receptor proteins in the brain, whereas top-down approaches consider predominantly cortical and thalamic network activity and connectivity. Both approaches have a number of explanatory gaps and as yet no unifying view has emerged. In addition to a direct interaction with primary target receptor proteins, general anesthetics have massive effects on neurotransmitter activity in the brain. They can change basal transmitter levels by interacting with neuronal activity, transmitter synthesis, release, reuptake and metabolism. By that way, they can affect a great number of neurotransmitter systems and receptors. Here, we review how different general anesthetics affect extracellular activity of neurotransmitters in the brain during induction, maintenance, and emergence from anesthesia and which functional consequences this may have. Commonalities and differences between different groups of anesthetics in their action on neurotransmitter activity are discussed. We also review how general anesthetics affect the response dynamics of the neurotransmitter systems after sensory stimulation. More than 30 years of research have now yielded a complex picture of the effects of general anesthetics on brain neurotransmitter basal activity and response dynamics. It is suggested that analyzing the effects on neurotransmitter activity is the logical next step after protein interactions in a bottom-up analysis of anesthetic action in the brain on the way to a unifying view of anesthesia. 相似文献
84.
Wilhelmina M. Huston Christopher J. Barker Anu Chacko Peter Timms 《Journal of bacteriology》2014,196(11):1915-1924
The chlamydiae are obligate intracellular parasites that have evolved specific interactions with their various hosts and host cell types to ensure their successful survival and consequential pathogenesis. The species Chlamydia pneumoniae is ubiquitous, with serological studies showing that most humans are infected at some stage in their lifetime. While most human infections are asymptomatic, C. pneumoniae can cause more-severe respiratory disease and pneumonia and has been linked to chronic diseases such as asthma, atherosclerosis, and even Alzheimer''s disease. The widely dispersed animal-adapted C. pneumoniae strains cause an equally wide range of diseases in their hosts. It is emerging that the ability of C. pneumoniae to survive inside its target cells, including evasion of the host''s immune attack mechanisms, is linked to the acquisition of key metabolites. Tryptophan and arginine are key checkpoint compounds in this host-parasite battle. Interestingly, the animal strains of C. pneumoniae have a slightly larger genome, enabling them to cope better with metabolite restrictions. It therefore appears that as the evolutionarily more ancient animal strains have evolved to infect humans, they have selectively become more “susceptible” to the levels of key metabolites, such as tryptophan. While this might initially appear to be a weakness, it allows these human C. pneumoniae strains to exquisitely sense host immune attack and respond by rapidly reverting to a persistent phase. During persistence, they reduce their metabolic levels, halting progression of their developmental cycle, waiting until the hostile external conditions have passed before they reemerge. 相似文献
85.
Juan Carlos Almagro Gary L Gilliland Felix Breden Jamie K Scott Devin Sok Matthias Pauthner Janice M Reichert Gustavo Helguera Raiees Andrabi Robert Mabry Mathieu Bléry James E Voss Juha Laurén Lubna Abuqayyas Stefan Barghorn Eshel Ben-Jacob James E Crowe James S Huston Stephen Albert Johnston Eric Krauland Fridtjof Lund-Johansen Wayne A Marasco Paul WHI Parren Kai Y Xu 《MABS-AUSTIN》2014,6(3):577-618
The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. 相似文献
86.
Esser R Müller T Stefes D Kloess S Seidel D Gillies SD Aperlo-Iffland C Huston JS Uherek C Schönfeld K Tonn T Huebener N Lode HN Koehl U Wels WS 《Journal of cellular and molecular medicine》2012,16(3):569-581
Treatment of high-risk neuroblastoma (NB) represents a major challenge in paediatric oncology. Alternative therapeutic strategies include antibodies targeting the disialoganglioside GD(2) , which is expressed at high levels on NB cells, and infusion of donor-derived natural killer (NK) cells. To combine specific antibody-mediated recognition of NB cells with the potent cytotoxic activity of NK cells, here we generated clonal derivatives of the clinically applicable human NK cell line NK-92 that stably express a GD(2) -specific chimeric antigen receptor (CAR) comprising an anti-GD(2) ch14.18 single chain Fv antibody fusion protein with CD3-ζ chain as a signalling moiety. CAR expression by gene-modified NK cells facilitated effective recognition and elimination of established GD(2) expressing NB cells, which were resistant to parental NK-92. In the case of intrinsically NK-sensitive NB cell lines, we observed markedly increased cell killing activity of retargeted NK-92 cells. Enhanced cell killing was strictly dependent on specific recognition of the target antigen and could be blocked by GD(2) -specific antibody or anti-idiotypic antibody occupying the CAR's cell recognition domain. Importantly, strongly enhanced cytotoxicity of the GD(2) -specific NK cells was also found against primary NB cells and GD(2) expressing tumour cells of other origins, demonstrating the potential clinical utility of the retargeted effector cells. 相似文献
87.
Two freshwater strains of the gammaproteobacterium Beggiatoa alba, B18LD and OH75-2a, are able to use methanol as a sole carbon and energy source under microoxic conditions. Genes encoding a methanol dehydrogenase large-subunit homolog and four enzymes of the tetrahydromethanopterin-dependent C1 oxidation pathway were identified in B18LD. No evidence of methanotrophy was detected. 相似文献
88.
89.
J C Marx V Blaise T Collins S D'Amico D Delille E Gratia A Hoyoux A L Huston G Sonan G Feller C Gerday 《Cellular and molecular biology, including cyto-enzymology》2004,50(5):643-655
Studies on psychrophilic enzymes to determine the structural features important for cold-activity have attracted increased attention in the last few years. This enhanced interest is due to the attractive properties of such proteins, i.e. a high specific activity and a low thermal stability, and thus, these enzymes constitute a tremendous potential for fundamental research and biotechnological applications. This review examines the impact of low temperatures on life, the diversity of adaptation to counteract these effects and gives an overview of the features proposed to account for low thermal stability and cold-activity, following the chronological order of the catalytic cycle phases. Moreover, we present an overview of recent techniques used in the analysis of the flexibility of a protein structure which is an important concept in cold-adaptation; an overview of biotechnological potential of psychrophilic enzymes and finally, a few frequently asked questions about cold-adaptation and their possible answers. 相似文献
90.
Y Deng J Zhao D Sakurai KM Kaufman JC Edberg RP Kimberly DL Kamen GS Gilkeson CO Jacob RH Scofield CD Langefeld JA Kelly ME Alarcón-Riquelme BIOLUPUS GENLES Networks JB Harley TJ Vyse BI Freedman PM Gaffney KM Sivils JA James TB Niewold RM Cantor W Chen BH Hahn EE Brown PROFILE BP Tsao 《Arthritis research & therapy》2012,14(Z3):A5