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981.
982.
983.
Joana Rocha Joe Sarkis Aline Thomas Laurence Pitou Jens Radzimanowski Magali Audry Valérie Chazalet Daniele de Sanctis Monica M. Palcic Maryse A. Block Agnès Girard‐Egrot Eric Maréchal Christelle Breton 《The Plant journal : for cell and molecular biology》2016,85(5):622-633
Monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) are the major lipid components of photosynthetic membranes, and hence the most abundant lipids in the biosphere. They are essential for assembly and function of the photosynthetic apparatus. In Arabidopsis, the first step of galactolipid synthesis is catalyzed by MGDG synthase 1 (MGD1), which transfers a galactosyl residue from UDP‐galactose to diacylglycerol (DAG). MGD1 is a monotopic protein that is embedded in the inner envelope membrane of chloroplasts. Once produced, MGDG is transferred to the outer envelope membrane, where DGDG synthesis occurs, and to thylakoids. Here we present two crystal structures of MGD1: one unliganded and one complexed with UDP. MGD1 has a long and flexible region (approximately 50 amino acids) that is required for DAG binding. The structures reveal critical features of the MGD1 catalytic mechanism and its membrane binding mode, tested on biomimetic Langmuir monolayers, giving insights into chloroplast membrane biogenesis. The structural plasticity of MGD1, ensuring very rapid capture and utilization of DAG, and its interaction with anionic lipids, possibly driving the construction of lipoproteic clusters, are consistent with the role of this enzyme, not only in expansion of the inner envelope membrane, but also in supplying MGDG to the outer envelope and nascent thylakoid membranes. 相似文献
984.
985.
A unique PE_PGRS protein inhibiting host cell cytosolic defenses and sustaining full virulence of Mycobacterium marinum in multiple hosts 下载免费PDF全文
Vipul K. Singh Laurence Berry Audrey Bernut Shubhra Singh Séverine Carrère‐Kremer Albertus Viljoen Laeticia Alibaud Laleh Majlessi Roland Brosch Vinita Chaturvedi Jeroen Geurtsen Michel Drancourt Laurent Kremer 《Cellular microbiology》2016,18(11):1489-1507
Despite intense research, PE_PGRS proteins still represent an intriguing aspect of mycobacterial pathogenesis. These cell surface proteins influence virulence in several pathogenic species, but their diverse and exact functions remain unclear. Herein, we focussed on a PE_PGRS member from Mycobacterium marinum, MMAR_0242, characterized by an extended and unique C‐terminal domain. We demonstrate that an M. marinum mutant carrying a transposon insertion in MMAR_0242 is highly impaired in its ability to replicate in macrophages and amoebae, because of its inability to inhibit lysosomal fusion. As a consequence, this mutant failed to survive intracellularly as evidenced by a reduced number of cytosolic actin tail‐forming bacteria and by quantitative electron microscopy, which mainly localized MMAR_0242::Tn within membrane‐defined vacuoles. Functional complementation studies indicated that the C‐terminus, but not the N‐terminal PE_PGRS domain, is required for intracellular growth/survival. In line with these findings, disruption of MMAR_0242 resulted in a highly attenuated virulence phenotype in zebrafish embryos, characterized by restricted bacterial loads and a failure to produce granulomas. Furthermore, expression of MMAR_0242 in Mycobacterium smegmatis, a non‐pathogenic species naturally deficient in PE_PGRS production, resulted in increased survival in amoebae with enhanced cytotoxic cell death and increased survival in infected mice with splenomegaly. Overall, these results indicate that MMAR_0242 is required for full virulence of M. marinum and sufficient to confer pathogenic properties to M. smegmatis. 相似文献
986.
Laurence Brown 《Ethnic and racial studies》2016,39(10):1812-1830
The release of data from the 2011 census fuelled a media storm over Britain's ethnic and immigrant composition, while at the same time a much less visible series of public debates developed over the scope, organization and purpose of government information-gathering centred on how the existing census could be replaced with ‘Big data’. It is therefore particularly timely to explore the political choices, ontological shifts and statistical challenges shaping the array of enumeration projects that have developed in contemporary Britain to identify, classify, and count immigrants and their descendants. This article analyses the relationships between holistic (horizontal) and single-purpose (vertical) approaches to racial statistics, and how these were affected by the standardizations of classification in 1962 and 1991. A range of state archives and contemporary accounts are used to examine the material practices and organizational tensions that fuelled the divergence, transfer and interaction of these attempts at racial legibility. 相似文献
987.
Barbara Da Costa Elodie Dumon Laurence Le Moigno Sylvie Bodard Pierre Castelnau Thierry Letellier Christophe Rocher 《Journal of bioenergetics and biomembranes》2016,48(5):483-491
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice have been widely used to model the loss of dopaminergic neurons. As this treatment leads to basal ganglia degeneration, it was proposed that MPTP mice could be used as a model of Leigh syndrome. However, this mitochondrial pathology is biochemically characterized by a respiratory chain dysfunction. To determine if MPTP can affect in vivo mitochondria function, we measured the activities of mitochondrial respiratory chain complexes in several tissues. Our results show that MPTP affects mainly mitochondrial respiratory chain complex IV, as found in Leigh Syndrome, confirming that acute MPTP intoxicated mice are a good model of Leigh Syndrome. 相似文献
988.
β cell membrane remodelling and procoagulant events occur in inflammation‐driven insulin impairment: a GLP‐1 receptor dependent and independent control 下载免费PDF全文
Céline Gleizes Guillaume Kreutter Malak Abbas Mohamad Kassem Andrei Alexandru Constantinescu Julie Boisramé‐Helms Blandine Yver Laurence Kessler 《Journal of cellular and molecular medicine》2016,20(2):231-242
Inflammation and hyperglycaemia are associated with a prothrombotic state. Cell‐derived microparticles (MPs) are the conveyors of active procoagulant tissue factor (TF) and circulate at high concentration in diabetic patients. Liraglutide, a glucagon‐like peptide (GLP)‐1 analogue, is known to promote insulin secretion and β‐cell preservation. In this in vitro study, we examined the link between insulin impairment, procoagulant activity and plasma membrane remodelling, under inflammatory conditions. Rin‐m5f β‐cell function, TF activity mediated by MPs and their modulation by 1 μM liraglutide were examined in a cell cross‐talk model. Methyl‐β‐cyclodextrine (MCD), a cholesterol depletor, was used to evaluate the involvement of raft on TF activity, MP shedding and insulin secretion as well as Soluble N‐éthylmaleimide‐sensitive‐factor Attachment protein Receptor (SNARE)‐dependent exocytosis. Cytokines induced a two‐fold increase in TF activity at MP surface that was counteracted by liraglutide. Microparticles prompted TF activity on the target cells and a two‐fold decrease in insulin secretion via protein kinase A (PKA) and p38 signalling, that was also abolished by liraglutide. Large lipid raft clusters were formed in response to cytokines and liraglutide or MCD‐treated cells showed similar patterns. Cells pre‐treated by saturating concentration of the GLP‐1r antagonist exendin (9‐39), showed a partial abolishment of the liraglutide‐driven insulin secretion and liraglutide‐decreased TF activity. Measurement of caspase 3 cleavage and MP shedding confirmed the contribution of GLP‐1r‐dependent and ‐independent pathways. Our results confirm an integrative β‐cell response to GLP‐1 that targets receptor‐mediated signalling and membrane remodelling pointing at the coupling of insulin secretion and inflammation‐driven procoagulant events. 相似文献
989.
Physical activity attenuates the effect of the FTO genotype on obesity traits in European adults: The Food4Me study 下载免费PDF全文
Carlos Celis‐Morales Cyril F.M. Marsaux Katherine M. Livingstone Santiago Navas‐Carretero Rodrigo San‐Cristobal Clare B. O'donovan Hannah Forster Clara Woolhead Rosalind Fallaize Anna L. Macready Silvia Kolossa Jacqueline Hallmann Lydia Tsirigoti Christina P. Lambrinou George Moschonis Magdalena Godlewska Agnieszka Surwio Keith Grimaldi Jildau Bouwman Yannis Manios Iwona Traczyk Christian A. Drevon Laurence D. Parnell Hannelore Daniel Eileen R. Gibney Lorraine Brennan Marianne C. Walsh Mike Gibney Julie A. Lovegrove J. Alfredo Martinez Wim H.M. Saris John C. Mathers 《Obesity (Silver Spring, Md.)》2016,24(4):962-969
990.
Véronique Morel Dominique Joly Christine Villatte Claude Dubray Xavier Durando Laurence Daulhac Catherine Coudert Delphine Roux Bruno Pereira Gisèle Pickering 《PloS one》2016,11(4)
BackgroundNeuropathic pain following surgical treatment for breast cancer with or without chemotherapy is a clinical burden and patients frequently report cognitive, emotional and quality of life impairment. A preclinical study recently showed that memantine administered before surgery may prevent neuropathic pain development and cognitive dysfunction. With a translational approach, a clinical trial has been carried out to evaluate whether memantine administered before and after mastectomy could prevent the development of neuropathic pain, the impairment of cognition and quality of life.MethodA randomized, pilot clinical trial included 40 women undergoing mastectomy in the Oncology Department, University Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) was administered for four weeks starting two weeks before surgery. The primary endpoint was pain intensity measured on a (0–10) numerical rating scale at three months post-mastectomy.ResultsData analyses were performed using mixed models and the tests were two-sided, with a type I error set at α = 0.05. Compared with placebo, patients receiving memantine showed at three months a significant difference in post-mastectomy pain intensity, less rescue analgesia and a better emotional state. An improvement of pain symptoms induced by cancer chemotherapy was also reported.ConclusionsThis study shows for the first time the beneficial effect of memantine to prevent post-mastectomy pain development and to diminish chemotherapy-induced pain symptoms. The lesser analgesic consumption and better well-being of patients for at least six months after treatment suggests that memantine could be an interesting therapeutic option to diminish the burden of breast cancer therapy.