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21.
Emanuela Anna Roselli Silvia Lazzati Federico Iseppon Massimiliano Manganini Livia Marcato Marzia Bruna Gariboldi Federico Maggi Francesca Romana Grati Giuseppe Simoni 《Cytotherapy》2013,15(11):1340-1351
Background aimsFirst-trimester chorionic villi (CV) are an attractive source of human mesenchymal stromal cells (hMSC) for possible applications in cellular therapy and regenerative medicine. Human MSC from CV were monitored for genetic stability in long-term cultures.MethodsWe set up a good manufacturing practice cryopreservation procedure for small amounts of native CV samples. After isolation, hMSC were in vitro cultured and analyzed for biological end points. Genome stability at different passages of expansion was explored by karyotype, genome-wide array-comparative genomic hybridization and microsatellite genotyping.ResultsGrowth curve analysis revealed a high proliferative potential of CV-derived cells. Immunophenotyping showed expression of typical MSC markers and absence of hematopoietic markers. Analysis of multilineage potential demonstrated efficient differentiation into adipocytes, osteocytes, chondrocytes and induction of neuro-glial commitment. In angiogenic experiments, differentiation in endothelial cells was detected by in vitro Matrigel assay after vascular endothelial growth factor stimulation. Data obtained from karyotyping, array-comparative genomic hybridization and microsatellite genotyping comparing early with late DNA passages did not show any genomic variation at least up to passage 10. Aneuploid clones appeared in four of 14 cases at latest passages, immediately before culture growth arrest.ConclusionsOur findings indicate that hCV-MSC are genetically stable in long-term cultures at least up to passage 10 and that it is possible to achieve clinically relevant amounts of hCV-MSC even after few stages of expansion. Genome abnormalities at higher passages can occasionally occur and are always associated with spontaneous growth arrest. Under these circumstances, hCV-MSC could be suitable for therapeutic purposes. 相似文献
22.
Laura Brunelli Giuseppe Ristagno Renzo Bagnati Francesca Fumagalli Roberto Latini Roberto Fanelli Roberta Pastorelli 《Metabolomics : Official journal of the Metabolomic Society》2013,9(4):839-852
The mechanisms responsible for post-resuscitation myocardial and cerebral dysfunction are not well understood, especially in the early post-resuscitation phases. In this investigation, we first adopted unbiased mass spectrometry-based metabolomic profiling to identify perturbations in circulating metabolites in a rat model of cardiac arrest and cardiopulmonary resuscitation. Our findings strongly indicated early alterations in a major route of the tryptophan catabolism, namely the kynurenines pathway, after resuscitation. Specific metabolites involved in the tryptophan catabolism were quantified absolutely using liquid chromatography-multiple reaction monitoring-mass spectrometry. Tryptophan plasma concentration fell significantly very early in the post-resuscitation phase, while its metabolites, l-kynurenine, kynurenic acid, 3-hydroxyanthranilic acid and 5-hydroxyindoleacetic acid, rose significantly. Changes in their concentration reflected changes in rat post-resuscitation myocardial dysfunction. Elevated plasma level of kynurenic acid, 3-hydroxyanthranilic acid were associated with significant decrease in ejection fraction and stroke volume. It is well known that kynurenines pathway is involved in the pathogenesis of numerous central nervous system disorders. By implication, altered levels of tryptophan metabolites in the early post resuscitation phase might contribute to the degree of cognitive recovery. Our results suggest that kynurenine pathway is activated early following resuscitation from cardiac arrest and might account for the severity of post-resuscitation syndrome. Our explorative investigation indicate that metabolomics can help to clarify unexplored biochemical pathways in cardiopulmonary resuscitation. 相似文献
23.
Stefano Toldo Rachel W. Goehe Marzia Lotrionte Eleonora Mezzaroma Evan T. Sumner Giuseppe G. L. Biondi-Zoccai Ignacio M. Seropian Benjamin W. Van Tassell Francesco Loperfido Giovanni Palazzoni Norbert F. Voelkel Antonio Abbate David A. Gewirtz 《PloS one》2013,8(3)
Purpose
The antineoplastic efficacy of anthracyclines is limited by their cardiac toxicity. In this study, we evaluated the toxicity of doxorubicin, non-pegylated liposomal-delivered doxorubicin, and epirubicin in HL-1 adult cardiomyocytes in culture as well as in the mouse in vivo.Methods
The cardiomyocytes were incubated with the three anthracyclines (1 µM) to assess reactive oxygen generation, DNA damage and apoptotic cell death. CF-1 mice (10/group) received doxorubicin, epirubicin or non-pegylated liposomal-doxorubicin (10 mg/kg) and cardiac function was monitored by Doppler echocardiography to measure left ventricular ejection fraction (LVEF), heart rate (HR) and cardiac output (CO) both prior to and 10 days after drug treatment.Results
In HL-1 cells, non-pegylated liposomal-doxorubicin generated significantly less reactive oxygen species (ROS), as well as less DNA damage and apoptosis activation when compared with doxorubicin and epirubicin. Cultured breast tumor cells showed similar sensitivity to the three anthracyclines. In the healthy mouse, non-pegylated liposomal doxorubicin showed a minimal and non-significant decrease in LVEF with no change in HR or CO, compared to doxorubicin and epirubicin.Conclusion
This study provides evidence for reduced cardiac toxicity of non-pegylated-liposomal doxorubicin characterized by attenuation of ROS generation, DNA damage and apoptosis in comparison to epirubicin and doxorubicin. 相似文献24.
Luiz Claudio Pereira Ribeiro Cassia Cristina Alves Gon?alves Carla Maria Sena Andrade Slater Silvia Maia Farias de Carvalho Marzia Puccioni-Sohler 《Memórias do Instituto Oswaldo Cruz》2013,108(6):730-734
Intrathecal synthesis of human T-lymphotropic virus type 1 (HTLV-1) antibodies
(Abs) represents conclusive evidence of a specific immune response in the
central nervous system of HTLV-1 associated myelopathy/tropical spastic
paraparesis (HAM/TSP) patients. Western blotting (WB) for HTLV Abs in serum is a
confirmatory test for HTLV-1 infection. The aim of this study was to standardise
the Western blot to demonstrate the intrathecal pattern of Abs against HTLV-1
proteins in HAM/TSP patients. Paired cerebrospinal fluid (CSF) and serum samples
were selected from 20 patients with definite HAM/TSP, 19 HTLV-1 seronegative
patients and two HTLV-1 patients without definite HAM/TSP. The presence of
reactive bands of greater intensity in the CSF compared to serum (or bands in
only the CSF) indicated the intrathecal synthesis of anti-HTLV-1 Abs. All
definite HAM/TSP patients presented with an intrathecal synthesis of anti-HTLV-1
Abs; these Abs were not detected in the control patients. The most frequent
intrathecal targets of anti-HTLV-1 Abs were GD21, rgp46-I and p24 and, to a
lesser extent, p19, p26, p28, p32, p36, p53 gp21 and gp46. The intrathecal
immune response against env (GD21 and rgp46-I) and
gag (p24) proteins represents the most important humoral
pattern in HAM/TSP. This response may be used as a diagnostic marker,
considering the frequent association of intrathecal anti-HTLV-1 Ab synthesis
with HAM/TSP and the pathogenesis of this neurological disease. 相似文献
25.
Francesco Castellani Valentina Ghidini Maria Carla Tafi Marzia Boaretti Maria M. Lleo 《Microbial ecology》2013,66(1):224-231
During the infectious process, pathogens may reach anatomical sites where they are exposed to substances interfering with their growth. These substances can include molecules produced by the host, and his resident microbial population, as well as exogenous antibacterial drugs. Suboptimal concentrations of inhibitory molecules and stress conditions found in vivo (high or low temperatures, lack of oxygen, extreme pH) might induce in bacteria the activation of survival mechanisms blocking their division capability but allowing them to stay alive. These “dormant” bacteria can be reactivated in particular circumstances and would be able to express their virulence traits. In this study, it was evaluated the effect of some environmental conditions, such as optimal and suboptimal temperatures, direct light and antibiotic sub-inhibitory concentrations doses of antibiotic, on the human pathogens Escherichia coli and Enterococcus faecalis when incubated in fluids accumulated in the body of patients with different pathologies. It is shown that inoculation in a number of accumulated body fluids and the presence of gentamicin, reliable conditions encountered during pathological states, induce stress-responding strategies enabling bacteria to persist in microcosms mimicking the human body. Significant differences were detected in Gram-negative and Gram-positive species with E. faecalis surviving, as starved or viable but non-culturable forms, in any microcosm and condition tested and E. coli activating a viable but non-culturable state only in some clinical samples. The persistence of bacteria under these conditions, being non-culturable, might explain some recurrent infections without isolation of the causative agent after application of the standard microbiological methods. 相似文献
26.
Marzia Boi Juan Antonio Llorens Lucas Cortés Gregorio Lladó Leonardo Llorens 《Grana》2013,52(2):93-105
Measurements and observations of pollen grains of varying structure before and after dehiscence of the anther sac illustrate large magnitudes of harmomegathic changes in volume and shape. Such changes are compared for colpate, porate, and colporate grains, and it is suggested that the nature of the harmomegathal action may serve to distinguish colpi or furrows from pores. Consideration of the requirement to allow harmomegathy while preventing wall collapse may provide at least partial explanation for evolution of the internal structure and external sculpturing of pollen grain walls. 相似文献
27.
Lucas Cunha Dias de Rezende Fernando Fumagalli Marraiana Schiavon Bortolin Marianne Garcia de Oliveira Murilo Helder de Paula Valter Ferreira de Andrade-Neto Flavio da Silva Emery 《Bioorganic & medicinal chemistry letters》2013,23(16):4583-4586
1,4-Naphthoquinone derivatives are known to have relevant activities against several parasites. Among the treatment options for malaria, atovaquone, a 1,4-naphthoquinone derivative, is widely applied in the treatment and prophylaxis of such disease. Based on the structure simplification of atovaquone, we designed and synthesized four novel naphthoquinoidal derivatives. The compounds were obtained by the underexplored epoxide-opening reaction of 1,4-naphthoquinone using aniline derivatives as nucleophiles. The antiplasmodial activity of the synthesized compounds was performed in vivo using Peter’s 4 days suppression test. Significant parasitemia reduction and increased survival were observed for some of the compounds. 相似文献
28.
Sonia Valdivia Cassia M. L. Ugaya Jutta Hildenbrand Marzia Traverso Bernard Mazijn Guido Sonnemann 《The International Journal of Life Cycle Assessment》2013,18(9):1673-1685
Purpose
To contribute to the upcoming United Nations Conference on Sustainable Development (Rio+20) in 2012 by introducing a life cycle sustainability assessment (LCSA) and showing how it can play a crucial role in moving towards sustainable consumption and production. The publication, titled Towards a Life Cycle Sustainability Assessment, and published by the UNEP/SETAC Life Cycle Initiative aims to show how three life cycle techniques—(environmental) LCA, S-LCA and LCC—can be combined as part of an over-arching LCSA.Methods
The method was demonstrated by evaluating the characteristics of each phase for each life cycle technique. In defining the goal and scope of an LCSA, for example, different aspects should be taken into account to establish the aim of the study as well as the functional unit, system boundaries, impact category and allocation. Then, the data to be collected for the life cycle sustainability inventory can be either in a unit process or on an organisational level. They can also be quantitative or qualitative. Life cycle sustainability impact assessment should consider the relevance of the impacts as well as the perspective of stakeholders. The interpretation should not add up the results, but rather evaluate them jointly. In order to clarify the approach, a case study is presented to evaluate three types of marble according to the proposed method.Results and discussion
The authors have identified that while LCSA is feasible, following areas need more development: data production and acquisition, methodological development, discussion about LCSA criteria (e.g. cutoff rules), definitions and formats of communication and dissemination of LCSA results and the expansion of research and applications combining (environmental) LCA, LCC and S-LCA. The authors also indicate that it is necessary to develop more examples and cases to improve user capacity to analyse the larger picture and therefore address the three dimensions or pillars of sustainability in a systematic way. Software and database providers are called for in order to facilitate user-friendly and accessible tools to promote LCSAs.Conclusions
The application demonstrated that, although methodological improvements are still needed, important steps towards an overarching sustainability assessment have been accomplished. LCSA is possible and should be pursued; however, more efforts should be made to improve the technique and facilitate the studies in order to contribute to a greener economy. 相似文献29.
Marzia Scortegagna Chelsea Ruller Surya K. De Elisa Barile Stan Krajewski Pedro Aza‐Blanc Roy Williams Anthony B. Pinkerton Michael Jackson Lynda Chin Maurizio Pellecchia Marcus Bosenberg Ze'ev A. Ronai 《Pigment cell & melanoma research》2013,26(1):136-142
To date, there are no effective therapies for tumors bearing NRAS mutations, which are present in 15–20% of human melanomas. Here we extend our earlier studies where we demonstrated that the small molecule BI‐69A11 inhibits the growth of melanoma cell lines. Gene expression analysis revealed the induction of interferon‐ and cell death‐related genes that were associated with responsiveness of melanoma cell lines to BI‐69A11. Strikingly, the administration of BI‐69A11 inhibited melanoma development in genetically modified mice bearing an inducible form of activated Nras and a deletion of the Ink4a gene (Nras(Q61K)::Ink4a?/?). Biweekly administration of BI‐69A11 starting at 10 weeks or as late as 24 weeks after the induction of mutant Nras expression inhibited melanoma development (100 and 36%, respectively). BI‐69A11 treatment did not inhibit the development of histiocytic sarcomas, which constitute about 50% of the tumors in this model. BI‐69A11‐resistant Nras(Q61K)::Ink4a?/? tumors exhibited increased CD45 expression, reflective of immune cell infiltration and upregulation of gene networks associated with the cytoskeleton, DNA damage response, and small molecule transport. The ability to attenuate the development of NRAS mutant melanomas supports further development of BI‐69A11 for clinical assessment. 相似文献
30.
Caterina Bason Renata Lorini Claudio Lunardi Marzia Dolcino Alessandro Giannattasio Giuseppe d’Annunzio Antonella Rigo Nicoletta Pedemonte Roberto Corrocher Antonio Puccetti 《PloS one》2013,8(2)
Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells. The role played by autoantibodies directed against beta cells antigens in the pathogenesis of the disease is still unclear. Coxsackievirus B infection has been linked to the onset of type 1 diabetes; however its precise role has not been elucidated yet. To clarify these issues, we screened a random peptide library with sera obtained from 58 patients with recent onset type 1 diabetes, before insulin therapy. We identified an immunodominant peptide recognized by the majority of individual patients’sera, that shares homology with Coxsackievirus B4 VP1 protein and with beta-cell specific autoantigens such as phogrin, phosphofructokinase and voltage-gated L-type calcium channels known to regulate beta cell apoptosis. Antibodies against the peptide affinity-purified from patients’ sera, recognized the viral protein and autoantigens; moreover, such antibodies induced apoptosis of the beta cells upon binding the L-type calcium channels expressed on the beta cell surface, suggesting a calcium dependent mechanism. Our results provide evidence that in autoimmune diabetes a subset of anti-Coxsackievirus antibodies are able to induce apoptosis of pancreatic beta cells which is considered the most critical and final step in the development of autoimmune diabetes without which clinical manifestations do not occur. 相似文献