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961.
Verónica Vidal Susana García-Cerro Paula Martínez Andrea Corrales Sara Lantigua Rebeca Vidal Noemí Rueda Laurence Ozmen Maria-Clemencia Hernández Carmen Martínez-Cué 《Molecular neurobiology》2018,55(6):4745-4762
Trisomy 21 or Down syndrome (DS) is the most common cause of intellectual disability of a genetic origin. The Ts65Dn (TS) mouse, which is the most commonly used and best-characterized mouse model of DS, displays many of the cognitive, neuromorphological, and biochemical anomalies that are found in the human condition. One of the mechanisms that have been proposed to be responsible for the cognitive deficits in this mouse model is impaired GABA-mediated inhibition. Because of the well-known modulatory role of GABAA α5 subunit-containing receptors in cognitive processes, these receptors are considered to be potential targets for improving the intellectual disability in DS. The chronic administration of GABAA α5-negative allosteric modulators has been shown to be procognitive without anxiogenic or proconvulsant side effects. In the present study, we use a genetic approach to evaluate the contribution of GABAA α5 subunit-containing receptors to the cognitive, electrophysiological, and neuromorphological deficits in TS mice. We show that reducing the expression of GABAA α5 receptors by deleting one or two copies of the Gabra5 gene in TS mice partially ameliorated the cognitive impairments, improved long-term potentiation, enhanced neural differentiation and maturation, and normalized the density of the GABAergic synapse markers. Reducing the gene dosage of Gabra5 in TS mice did not induce motor alterations and anxiety or affect the viability of the mice. Our results provide further evidence of the role of GABAA α5 receptor-mediated inhibition in cognitive impairment in the TS mouse model of DS. 相似文献
962.
Immunological impact of Wharton’s Jelly mesenchymal stromal cells and natural killer cell co-culture
Mehdi Najar Mohammad Fayyad-Kazan Nathalie Meuleman Dominique Bron Hussein Fayyad-Kazan Laurence Lagneaux 《Molecular and cellular biochemistry》2018,438(1-2):111-121
In palmipeds, overfeeding leads to hepatic steatosis, also called “foie gras” which is the result of many metabolic mechanisms. In order to understand these mechanisms, we decided to measure the expression of genes implicated in lipid metabolism during 12 hours (h) following the last meal of the overfeeding period. We have shown that there is a precocious expression (within 2 h) of fatty acid synthase and acyl CoA synthetase long-chain 1 in liver and muscle of mule ducks in addition with a later peak. Furthermore, di-acyl glycerol acyl transferase presents the highest induction of expression in liver and it is overexpressed quite a long time, positioning this enzyme as a key factor in hepatic steatosis. These observations are quite similar in muscle. Lipoprotein secretion is upregulated later in postprandial period, with an upregulation of apolipoprotein and microsomal triglycerides transfer protein beginning at 5 h in liver or muscle. Regarding hepatic re-uptake of lipid, lesser variations are observed, suggesting that fatty acid binding protein and very low-density lipoprotein receptor (VLDLR) are already at their maximum expression specifically in these tissues. In muscle, VLDLR and LDLR upregulation is observed 5 h after the meal, associated with an overexpression in the adipose tissue of lipase maturation factor 1 involved in the maturation of lipoprotein lipase. These findings will allow us to better understand the kinetic treatment in lipid metabolism after a meal in overfed ducks. This first report on kinetic expression will allow researcher to better target their sampling time knowing the optimal point of expression of each gene. 相似文献
963.
Endogenous Stochastic Decoding of the CUG Codon by Competing Ser- and Leu-tRNAs in Ascoidea asiatica
Stefanie Mühlhausen Hans Dieter Schmitt Kuan-Ting Pan Uwe Plessmann Henning Urlaub Laurence D. Hurst Martin Kollmar 《Current biology : CB》2018,28(13):2046-2057.e5
964.
965.
Functional analysis of Toxoplasma lactate dehydrogenases suggests critical roles of lactate fermentation for parasite growth in vivo 下载免费PDF全文
Ningbo Xia Jichao Yang Shu Ye Lihong Zhang Yanqin Zhou Junlong Zhao Laurence David Sibley Bang Shen 《Cellular microbiology》2018,20(1)
Glycolysis was thought to be the major pathway of energy supply in both fast‐replicating tachyzoites and slowly growing bradyzoites of Toxoplasma gondii. However, its biological significance has not been clearly verified. The genome of T. gondii encodes two lactate dehydrogenases (LDHs), which are differentially expressed in tachyzoites and bradyzoites. In this study, we knocked out the two LDH genes individually and in combination and found that neither gene was required for tachyzoite growth in vitro under standard growth conditions. However, during infection in mice, Δldh1 and Δldh1 Δldh2 mutants were unable to propagate and displayed significant virulence attenuation and cyst formation defects. LDH2 only played minor roles in these processes. To further elucidate the mechanisms underlying the critical requirement of LDH in vivo, we found that Δldh1 Δldh2 mutants replicated significantly more slowly than wild‐type parasites when cultured under conditions with physiological levels of oxygen (3%). In addition, Δldh1 Δldh2 mutants were more susceptible to the oxidative phosphorylation inhibitor oligomycin A. Together these results suggest that lactate fermentation is critical for parasite growth under physiological conditions, likely because energy production from oxidative phosphorylation is insufficient when oxygen is limited and lactate fermentation becomes a key supplementation. 相似文献
966.
Krista Revert Laurence Audran Jocelyne Pengam Pascal Lesne Dominique Pougheon Bertrand 《Orphanet journal of rare diseases》2018,13(1):8
Background
The Cystic Fibrosis (CF) center in Roscoff (Brittany) has been involved in therapeutic education programs (TEP) since 2006 and took part in the pilot phase of the French quality improvement program (QIP) since 2011. The aim was to improve the nutritional status of children with cystic fibrosis aged 2-12 years old in order to optimize their health status as they enter adolescence.Methods
A multidisciplinary quality team was created in order to select and address a specific health problem among our pediatric population. Following analysis of yearly indicators for our CF center, our team chose to improve quality of care concerning nutritional status of children aged 2-12 years old. Factors influencing efficacy were studied, tools were developed to implement a new nutritional program, results were analyzed on a real-time basis.Results
Over the 3 year period, all patients from 2 years of age, were monitored with the new follow-up program (2012: N =?34; 2014: N =?44). Each patient was followed up at every clinic visit, their BMI z-score was calculated to decide their nutritional risk and personalize their follow-up program consequently. Between 1/1/2012 and 31/12/2014, the mean BMI z-score of the open cohort improved from ?0.49 to ?0.22.Conclusions
Since 2014, focus on nutrition using the newly-adapted program has become routine practice at each follow-up visit. Patients and parents expressed a high level of satisfaction (75% very satisfied). The follow-up program aimed at improving nutritional status for children aged 2-12 years old was successfully implemented and integrated into routine practice; it was therefore extended to all children with CF (1 month - 18 years) in our center. The relationship among professional and patients and parents was strengthened.967.
Chantal Andre Marie-Claude Guillemin Jun Zhu Marcel H. M. Koken Frdrique Quignon Laurence Herve Mounira K. Chelbi-Alix Daniel Dhumeaux Zeng-Yi Wang Laurent Degos Zhu Chen Hugues de The 《Experimental cell research》1996,229(2):253
Acute promyelocytic leukemia (APL) is specifically associated to a t(15; 17) translocation which fuses a gene encoding a nuclear receptor for retinoic acid, RARα, to a previously unknown gene PML. The PML protein is localized in the nucleus on a specific domain of unknown function (PML nuclear bodies, NB) previously detected with autoimmune sera from patients with primary biliary cirrhosis (PBC). These bodies are nuclear matrix-associated and all of their identified components (PML, Sp100, and NDP52) are sharply upregulated by interferons. We show that autoantibodies against both PML and Sp100 are usually associated in sera with multiple nuclear dot anti-nuclear antibodies and demonstrate that PML is an autoantigen, not only in PBC, but also in other autoimmune diseases. In APL, the PML/RARα fusion interferes with both the retinoic acid (RA) response and PML localization on nuclear bodies, but the respective contribution of each defect to leukemogenesis is unclear. RA induces the terminal differentiation of APL blasts, yielding to complete remissions, and corrects the localization of NB antigens. Arsenic trioxide (As2O3) also induces remissions in APL, seemingly through induction of apoptosis. We show that in APL, As2O3leads to the rapid reformation of PML bodies. Thus, both agents correct the defect in NB antigen localization, stressing the role of nuclear bodies in the pathogenesis of APL. 相似文献
968.
Development of two PCR assays for the identification of mycoplasmas causing contagious agalactia 总被引:1,自引:0,他引:1
Laurence Dedieu Viviane Mady Pierre-Charles Lefevre 《FEMS microbiology letters》1995,129(2-3):243-249
Abstract A new detection test for the mycoplasmas causing contagious agalactia, Mycoplasma agalactiae , M. capricolum subsp. capricolum and M. mycoides subsp. mycoldes L.C., was developed. It was based on two polymerase chain reaction assays: the Ma-PCR for the detection of M. agalactiae and the MYC-PCR for the 'mycoides cluster' thus including M. capricolum subsp. capricolum and M. mycoides subsp. mycoides L.C. An M. agalactiae strain was identified by a 933-bp Ma-PCR product and no amplification with the MYC-PCR. In contrast, a 460-bp MYC-PCR product and a negative or a 350-bp Ma-PCR product characterized a 'mycoides cluster' strain. M. capricolum subsp. capricolum and M. mycoides subsp. mycoides L.C. were identified by their species-specific Asel pattern of the 460-bp MYC-PCR product. 相似文献
969.
Anne Nègre-Salvayre Laurence Mabile Jean Delchambre Robert Salvayre 《Biological trace element research》1995,47(1-3):81-91
Low-density lipoproteins (LDL) mildly oxidized by copper ions or UV radiations exhibit a cytotoxic effect to cultured endothelial
cells. Rutin, a polyphenolic flavonoid, ascorbic acid, and α-tocopherol were able to inhibit the peroxidation of LDL and their
subsequent cytotoxicity. The mixture of the three compounds (rutin/ascorbic acid/α-tocopherol, 4/4/1) exhibited a supra-additive
antioxidant effect. The inhibition of the cytotoxic effect was well correlated with that of TBARS formation. Another important
conclusion is that these antioxidants were able to prevent directly at the cellular level the cytotoxic effect of oxidized
LDL, since cells preincubated with them were protected against the cytotoxic effect of previously oxidized LDL. The protective
effect of antioxidants was limited because of their own toxicity. The antioxidant mixture permitted a maximal cytoprotective
effect with relatively lower concentrations to be obtained and the cytotoxicity of high concentrations to be avoided. In conclusion,
rutin, ascorbic acid, and α-tocopherol constitute two lines of defense in protecting cells against injury owing to oxidation
of LDL (1) at the LDL level, by inhibiting the LDL oxidation and the subsequent cytotoxicity, and (2) at the cellular level,
by protecting the cells directly, i.e., by increasing their resistance against the cytotoxic effect of oxidized LDL. 相似文献
970.