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991.
Ismail Iraqui Yasmina Chekkal Nada Jmari Violena Pietrobon Karine Fréon Audrey Costes Sarah A. E. Lambert 《PLoS genetics》2012,8(10)
Homologous recombination is a universal mechanism that allows repair of DNA and provides support for DNA replication. Homologous recombination is therefore a major pathway that suppresses non-homology-mediated genome instability. Here, we report that recovery of impeded replication forks by homologous recombination is error-prone. Using a fork-arrest-based assay in fission yeast, we demonstrate that a single collapsed fork can cause mutations and large-scale genomic changes, including deletions and translocations. Fork-arrest-induced gross chromosomal rearrangements are mediated by inappropriate ectopic recombination events at the site of collapsed forks. Inverted repeats near the site of fork collapse stimulate large-scale genomic changes up to 1,500 times over spontaneous events. We also show that the high accuracy of DNA replication during S-phase is impaired by impediments to fork progression, since fork-arrest-induced mutation is due to erroneous DNA synthesis during recovery of replication forks. The mutations caused are small insertions/duplications between short tandem repeats (micro-homology) indicative of replication slippage. Our data establish that collapsed forks, but not stalled forks, recovered by homologous recombination are prone to replication slippage. The inaccuracy of DNA synthesis does not rely on PCNA ubiquitination or trans-lesion-synthesis DNA polymerases, and it is not counteracted by mismatch repair. We propose that deletions/insertions, mediated by micro-homology, leading to copy number variations during replication stress may arise by progression of error-prone replication forks restarted by homologous recombination. 相似文献
992.
Karine Baumstarck Fran?oise Reuter Mohamed Boucekine Valérie Aghababian Irina Klemina Anderson Loundou Jean Pelletier Pascal Auquier 《PloS one》2012,7(12)
Background
Memory disturbances, in particular episodic verbal memory dysfunction, are the most frequent cognitive impairment observed in multiple sclerosis (MS) patients. The use of self-reported outcomes for evaluating treatment and managing care of these subjects has been questioned. The aim of this study was to provide new evidence about the suitability of self-reported outcomes for use in this impaired population by exploring the internal structure, reliability and external validity of a specific quality of life (QoL) instrument, the Multiple Sclerosis International Quality of Life questionnaire (MusiQoL).Methods
Design: cross-sectional study. Inclusion criteria: MS patients of any disease subtype. Data collection: sociodemographic (age, gender, marital status, education level, and occupational activity) and clinical data (MS subtype, Expanded Disability Status Scale, disease duration); QoL (MusiQoL and SF36); and memory performance (Grober and Buschke test). In accordance with the French norms of the memory test, non-impaired and impaired populations were defined for short- and long-delay free composites and for short- and long-delay total composites. For the 8 populations, psychometric properties were compared to those reported from the reference population assessed in the validation study.Principal Findings
One hundred and twenty-four consecutive patients were enrolled. The analysis performed in the impaired populations showed that the questionnaire structure adequately matched the initial structure of the MusiQoL. The unidimensionality of the dimensions was preserved, and the internal/external validity indices were close to those of the reference population.Conclusions/Significance
Our study suggests that memory dysfunction did not compromise the reliability or validity of the self-reported QoL questionnaires. 相似文献993.
Sadia Benamrouz Karine Guyot Sophie Gazzola Anthony Mouray Thierry Chassat Baptiste Delaire Magali Chabé Pierre Gosset Eric Viscogliosi Eduardo Dei-Cas Colette Creusy Valerie Conseil Gabriela Certad 《PloS one》2012,7(12)
Dexamethasone (Dex) treated Severe Combined Immunodeficiency (SCID) mice were previously described as developing digestive adenocarcinoma after massive infection with Cryptosporidium parvum as soon as 45 days post-infection (P.I.). We aimed to determine the minimum number of oocysts capable of inducing infection and thereby gastrointestinal tumors in this model. Mice were challenged with calibrated oocyst suspensions containing intended doses of: 1, 10, 100 or 105 oocysts of C. parvum Iowa strain. All administered doses were infective for animals but increasing the oocyst challenge lead to an increase in mice infectivity (P = 0.01). Oocyst shedding was detected at 7 days P.I. after inoculation with more than 10 oocysts, and after 15 days in mice challenged with one oocyst. In groups challenged with lower inocula, parasite growth phase was significantly higher (P = 0.005) compared to mice inoculated with higher doses. After 45 days P.I. all groups of mice had a mean of oocyst shedding superior to 10,000 oocyst/g of feces. The most impressive observation of this study was the demonstration that C. parvum-induced digestive adenocarcinoma could be caused by infection with low doses of Cryptosporidium, even with only one oocyst: in mice inoculated with low doses, neoplastic lesions were detected as early as 45 days P.I. both in the stomach and ileo-caecal region, and these lesions could evolve in an invasive adenocarcinoma. These findings show a great amplification effect of parasites in mouse tissues after challenge with low doses as confirmed by quantitative PCR. The ability of C. parvum to infect mice with one oocyst and to develop digestive adenocarcinoma suggests that other mammalian species including humans could be also susceptible to this process, especially when they are severely immunocompromised. 相似文献
994.
Raymond K Faraldo MM Deugnier MA Glukhova MA 《Seminars in cell & developmental biology》2012,23(5):599-605
Integrins are ubiquitously expressed major cell surface receptors for extracellular matrix. Integrin interaction with their extracellular ligands triggers activation of the intracellular signaling pathways that control cell shape, motility, proliferation, survival, cell-type-specific gene expression. In this review, we summarize recent studies analyzing contribution of integrins to the control of the mammary morphogenesis and differentiation, function and maintenance of mammary stem and progenitor cells and resume the data from mouse models revealing the contribution of the integrin-mediated signaling to mammary tumorigenesis. 相似文献
995.
Karine Malagu Heather Duggan Keith Menear Marc Hummersone Sylvie Gomez Christine Bailey Peter Edwards Jan Drzewiecki Frédéric Leroux Mar Jimenez Quesada Gesine Hermann Stephanie Maine Carrie-Anne Molyneaux Armelle Le Gall James Pullen Ian Hickson Lisa Smith Sharon Maguire Niall Martin Graeme Smith Martin Pass 《Bioorganic & medicinal chemistry letters》2009,19(20):5950-5953
We describe a novel series of potent inhibitors of the kinase activity of mTOR. The compounds display good selectivity relative to other PI3K-related kinase family members and, in cellular assays, inhibit both mTORC1 and mTORC2 complexes and exhibit good antiproliferative activity. 相似文献
996.
Frdric Catez Monique Erard Nathalie Schaerer-Uthurralt Karine Kindbeiter Jean-Jacques Madjar Jean-Jacques Diaz 《Molecular and cellular biology》2002,22(4):1126-1139
By microinjecting purified glutathione S-transferase linked to all or parts of herpes simplex virus type 1 US11 protein into either the nucleus or the cytoplasm, we have demonstrated that this nucleolar protein exhibits a new type of localization signal controlling both retention in nucleoli and export to the cytoplasm. Saturated mutagenesis combined with computer modeling allowed us to draw the fine-structure map of this domain, revealing a new proline-rich motif harboring both activities, which are temperature dependent and regulated by phosphorylation. Finally, crossing the nuclear pore complex from the cytoplasm to the nucleus is an energy-dependent process for US11 protein, while getting to nucleoli through the nucleoplasm is energy independent. 相似文献
997.
Karine Spiegel Laurence Weibel Claude Gronfier Gabrielle Brandenberger Marguerite Follenius 《Chronobiology international》1996,13(4):283-293
In addition to sleep processes, it has been suggested that an intrinsic circadian rhythmicity is involved in the temporal organization of prolactin (PRL) secretion. Eight night workers were studied to determine whether the PRL rhythm is adapted to their rest-activity schedule and whether this provides evidence in favor of an endogenous clock-driven component. Ten day-active subjects, sleeping once during the night and once after an 8-h delay in their sleep period, were used as a control group. Plasma PRL, body temperature, and plasma melatonin were measured at 10-min intervals. Twenty-four-hour PRL profiles did not differ between night workers sleeping as usual during the daytime and day-active subjects submitted to an abrupt sleep shift to daytime. For the two groups of subjects a transient PRL peak, similar in size and time of occurrence, was observed during the night. Melatonin, a strong marker of the primary circadian oscillator, displayed a phase shift that differed widely among night workers. Body temperature, on the other hand, was found to be more regularly adapted despite the persistence of a small decrease or leveling off during the night. Although no relationship was found between the melatonin increase and the nocturnal PRL peak, a concomitance with this transient temperature decrease could be demonstrated. The persistence of this PRL peak in night workers raises the question of its significance. (Chronobiology International, 13(4), 283-293, 1996) 相似文献
998.
P Sébert L Barthélémy Y Dietman C Douguet J Boulay 《European journal of applied physiology and occupational physiology》1990,61(3-4):271-273
A simple and cheap device has been designed which makes it possible to quantify a vertical jump. The parameters which can be measured or calculated with this device include: height of the jump, duration of thrust, maximal velocity and thus the corresponding maximal power output. The device was tested on 22 young soccer players for whom the height of the jump (0.47 m, SEM 0.015) and maximal power output (34.9 W. kg-1, SEM 1.04) were considered. The device is proposed for assessing training methods and sports aptitude. 相似文献
999.
Jing Wang William Rennie Chaochun Liu Charles S. Carmack Karine Prévost Marie-Pier Caron Eric Massé Ye Ding Joseph T. Wade 《Nucleic acids research》2015,43(21):10308-10320
Bacteria express large numbers of non-coding, regulatory RNAs known as ‘small RNAs’ (sRNAs). sRNAs typically regulate expression of multiple target messenger RNAs (mRNAs) through base-pairing interactions. sRNA:mRNA base-pairing often results in altered mRNA stability and/or altered translation initiation. Computational identification of sRNA targets is challenging due to the requirement for only short regions of base-pairing that can accommodate mismatches. Experimental approaches have been applied to identify sRNA targets on a genomic scale, but these focus only on those targets regulated at the level of mRNA stability. Here, we utilize ribosome profiling (Ribo-seq) to experimentally identify regulatory targets of the Escherichia coli sRNA RyhB. We not only validate a majority of known RyhB targets using the Ribo-seq approach, but also discover many novel ones. We further confirm regulation of a selection of known and novel targets using targeted reporter assays. By mutating nucleotides in the mRNA of a newly discovered target, we demonstrate direct regulation of this target by RyhB. Moreover, we show that Ribo-seq distinguishes between mRNAs regulated at the level of RNA stability and those regulated at the level of translation. Thus, Ribo-seq represents a powerful approach for genome-scale identification of sRNA targets. 相似文献
1000.
Free and nanoencapsulated vitamin D3: effects on E‐NTPDase and E‐ADA activities in an animal model with induced arthritis 下载免费PDF全文
Karine Lanes da Silveira Leonardo Lanes da Silveira Maria Luiza Prates Thorstenberg Fernanda Licker Cabral Livia Gelain Castilhos João Felipe Peres Rezer Diego Fontana de Andrade Ruy Carlos Ruver Beck Heloísa Einloft Palma Cinthia Melazzo de Andrade Renata da Silva Pereira Nara Maria Beck Martins Claudia de Mello Bertonchel dos Santos Daniela Bitencourt Rosa Leal 《Cell biochemistry and function》2016,34(4):262-273