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71.
Casalino L Magnani D De Falco S Filosa S Minchiotti G Patriarca EJ De Cesare D 《Molecular biotechnology》2012,50(3):171-180
The use of Embryonic Stem Cells (ESCs) holds considerable promise both for drug discovery programs and the treatment of degenerative
disorders in regenerative medicine approaches. Nevertheless, the successful use of ESCs is still limited by the lack of efficient
control of ESC self-renewal and differentiation capabilities. In this context, the possibility to modulate ESC biological
properties and to obtain homogenous populations of correctly specified cells will help developing physiologically relevant
screens, designed for the identification of stem cell modulators. Here, we developed a high throughput screening-suitable
ESC neural differentiation assay by exploiting the Cell
maker robotic platform and demonstrated that neural progenies can be generated from ESCs in complete automation, with high standards
of accuracy and reliability. Moreover, we performed a pilot screening providing proof of concept that this assay allows the
identification of regulators of ESC neural differentiation in full automation. 相似文献
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Cornelia Di Gaetano Floriana Voglino Simonetta Guarrera Giovanni Fiorito Fabio Rosa Anna Maria Di Blasio Paola Manzini Irma Dianzani Marta Betti Daniele Cusi Francesca Frau Cristina Barlassina Dario Mirabelli Corrado Magnani Nicola Glorioso Stefano Bonassi Alberto Piazza Giuseppe Matullo 《PloS one》2012,7(9)
In spite of the common belief of Europe as reasonably homogeneous at genetic level, advances in high-throughput genotyping technology have resolved several gradients which define different geographical areas with good precision. When Northern and Southern European groups were considered separately, there were clear genetic distinctions. Intra-country genetic differences were also evident, especially in Finland and, to a lesser extent, within other European populations. Here, we present the first analysis using the 125,799 genome-wide Single Nucleotide Polymorphisms (SNPs) data of 1,014 Italians with wide geographical coverage. We showed by using Principal Component analysis and model-based individual ancestry analysis, that the current population of Sardinia can be clearly differentiated genetically from mainland Italy and Sicily, and that a certain degree of genetic differentiation is detectable within the current Italian peninsula population. Pair-wise FST statistics Northern and Southern Italy amounts approximately to 0.001 between, and around 0.002 between Northern Italy and Utah residents with Northern and Western European ancestry (CEU). The Italian population also revealed a fine genetic substructure underscoring by the genomic inflation (Sardinia vs. Northern Italy = 3.040 and Northern Italy vs. CEU = 1.427), warning against confounding effects of hidden relatedness and population substructure in association studies. 相似文献
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Svenson KL Ahituv N Durgin RS Savage H Magnani PA Foreman O Paigen B Peters LL 《Journal of lipid research》2008,49(11):2452-2462
In an effort to discover new mouse models of cardiovascular disease using N-ethyl-N-nitrosourea (ENU) mutagenesis followed by high-throughput phenotyping, we have identified a new mouse mutation, C699Y, in the LDL receptor (Ldlr), named wicked high cholesterol (WHC). When WHC was compared with the widely used Ldlr knockout (KO) mouse, notable phenotypic differences between strains were observed, such as accelerated atherosclerotic lesion formation and reduced hepatosteatosis in the ENU mutant after a short exposure to an atherogenic diet. This loss-of-function mouse model carries a single base mutation in the Ldlr gene on an otherwise pure C57BL/6J (B6) genetic background, making it a useful new tool for understanding the pathophysiology of atherosclerosis and for evaluating additional genetic modifiers regulating hyperlipidemia and atherogenesis. Further investigation of genomic differences between the ENU mutant and KO strains may reveal previously unappreciated sequence functionality. 相似文献
77.
Neri M Ugolini D Dianzani I Gemignani F Landi S Cesario A Magnani C Mutti L Puntoni R Bonassi S 《Mutation research》2008,659(1-2):126-136
Exposure to asbestos fibers is a major risk factor for malignant pleural mesothelioma (MPM), lung cancer, and other non-neoplastic conditions, such as asbestosis and pleural plaques. However, in the last decade many studies have shown that polymorphism in the genes involved in xenobiotic and oxidative metabolism or in DNA repair processes may play an important role in the etiology and pathogenesis of these diseases. To evaluate the association between diseases linked to asbestos and genetic variability we performed a review of studies on this topic included in the PubMed database. One hundred fifty-nine citations were retrieved; 24 of them met the inclusion criteria and were evaluated in the review. The most commonly studied GSTM1 polymorphism showed for all asbestos-linked diseases an increased risk in association with the null genotype, possibly linked to its role in the conjugation of reactive oxygen species. Studies focused on GSTT1 null and SOD2 Ala16Val polymorphisms gave conflicting results, while promising results came from studies on alpha1-antitrypsin in asbestosis and MPO in lung cancer. Among genetic polymorphisms associated to the risk of MPM, the GSTM1 null genotype and two variant alleles of XRCC1 and XRCC3 showed increased risks in a subset of studies. Results for the NAT2 acetylator status, SOD2 polymorphism and EPHX activity were conflicting. Major limitations in the study design, including the small size of study groups, affected the reliability of these studies. Technical improvements such as the use of high-throughput techniques will help to identify molecular pathways regulated by candidate genes. 相似文献
78.
Galluzzi L Bertozzini E Penna A Perini F Pigalarga A Graneli E Magnani M 《Letters in applied microbiology》2008,46(2):261-266
Aims: The ichthyotoxic species Prymnesium parvum (Haptophyceae) is difficult to quantify in a microscopy‐based monitoring programme, because the cells are very small, fragile and their morphology can be distorted by the use of fixatives. In the attempt to overcome these problems, a real‐time PCR‐based method for the rapid and sensitive identification and quantification of P. parvum was developed. Methods and Results: A quantitative real‐time PCR assay was optimized with primers designed on the internal transcribed spacer 2 rDNA region of P. parvum. This PCR assay was specific, showing no amplification of DNA extracted from closely related species, and sensitive. Moreover, this method was able to detect and reliably quantify P. parvum cells in preserved environmental samples artificially spiked with known amounts of cultured cells. Conclusions: Considering the specificity, sensitivity and applicability to preserved environmental samples, this method may be a useful tool for the monitoring of this toxic species. Significance and Impact of the Study: The real‐time PCR method described in this study may represent a progress towards the rapid detection and quantification of P. parvum cells in water‐monitoring programmes, allowing the early application of strategies to control bloom events, such as the use of clay minerals. 相似文献
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