全文获取类型
收费全文 | 1086篇 |
免费 | 88篇 |
国内免费 | 1篇 |
学科分类
工业技术 | 1175篇 |
出版年
2024年 | 2篇 |
2023年 | 20篇 |
2022年 | 173篇 |
2021年 | 177篇 |
2020年 | 38篇 |
2019年 | 36篇 |
2018年 | 47篇 |
2017年 | 29篇 |
2016年 | 53篇 |
2015年 | 40篇 |
2014年 | 52篇 |
2013年 | 70篇 |
2012年 | 56篇 |
2011年 | 89篇 |
2010年 | 47篇 |
2009年 | 38篇 |
2008年 | 36篇 |
2007年 | 30篇 |
2006年 | 27篇 |
2005年 | 26篇 |
2004年 | 19篇 |
2003年 | 10篇 |
2002年 | 9篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 5篇 |
1996年 | 7篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有1175条查询结果,搜索用时 22 毫秒
31.
Lucia Marsich Alessio Ferluga Norman Venturini Marco Caniato Orfeo Sbaizero Chiara Schmid 《Polymer Engineering and Science》2016,56(7):727-734
In the field of self‐reinforced composites many researchers have focused their attention on the coextruded tapes composed of polypropylene core and PP/PE copolymer skin. Two similar commercial fabrics (P and T) have been compared in respect of their peel resistance. For both materials, peel resistance has a periodic trend that regularly follows fabric weave style. T has demonstrated an average peel resistance and a well‐bonded area slightly greater than P. Skin/core interfacial properties have been investigated and a crosscheck between differential scanning calorimetry (DSC) and Raman spectroscopy has been adopted to understand the influence of skin structure on consolidated laminate. DSC curves exhibit three melting peaks during first heating for both fabrics, corresponding to copolymer, skin/core interface, and core melting. After consolidation at 140°C stretching‐induced superstructure and PP crystallinity degree are preserved. The presence of PP/PE copolymer + PE blend only in fabric P has been pointed out and PE content has been calculated. POLYM. ENG. SCI., 56:727–734, 2016. © 2016 Society of Plastics Engineers 相似文献
32.
Identification and Structure–Activity Relationship Studies of Small‐Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1 下载免费PDF全文
Dr. Dina Robaa Dr. Tobias Wagner Chiara Luise Dr. Luca Carlino Joel McMillan Dr. Ralf Flaig Prof. Dr. Roland Schüle Prof. Dr. Manfred Jung Prof. Dr. Wolfgang Sippl 《ChemMedChem》2016,11(20):2327-2338
The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small‐molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure‐ and ligand‐based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4‐aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series. 相似文献
33.
34.
Maria Lucia Iacovino Chiara Carmen Miceli Marco De Felice Biagio Barone Luca Pompella Francesco Chiancone Erika Di Zazzo Giuseppe Tirino Carminia Maria Della Corte Ciro Imbimbo Ferdinando De Vita Felice Crocetto 《International journal of molecular sciences》2022,23(3)
Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum–Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification. 相似文献
35.
Chiara Cipollina Andreina Bruno Salvatore Fasola Marta Cristaldi Bernardo Patella Rosalinda Inguanta Antonio Vilasi Giuseppe Aiello Stefania La Grutta Claudia Torino Elisabetta Pace 《International journal of molecular sciences》2022,23(3)
Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds. 相似文献
36.
Elisa Rumi Chiara Trotti Daniele Vanni Ilaria Carola Casetti Daniela Pietra Emanuela SantAntonio 《International journal of molecular sciences》2020,21(23)
Among classical BCR-ABL-negative myeloproliferative neoplasms (MPN), primary myelofibrosis (PMF) is the most aggressive subtype from a clinical standpoint, posing a great challenge to clinicians. Whilst the biological consequences of the three MPN driver gene mutations (JAK2, CALR, and MPL) have been well described, recent data has shed light on the complex and dynamic structure of PMF, that involves competing disease subclones, sequentially acquired genomic events, mostly in genes that are recurrently mutated in several myeloid neoplasms and in clonal hematopoiesis, and biological interactions between clonal hematopoietic stem cells and abnormal bone marrow niches. These observations may contribute to explain the wide heterogeneity in patients’ clinical presentation and prognosis, and support the recent effort to include molecular information in prognostic scoring systems used for therapeutic decision-making, leading to promising clinical translation. In this review, we aim to address the topic of PMF molecular genetics, focusing on four questions: (1) what is the role of mutations on disease pathogenesis? (2) what is their impact on patients’ clinical phenotype? (3) how do we integrate gene mutations in the risk stratification process? (4) how do we take advantage of molecular genetics when it comes to treatment decisions? 相似文献
37.
38.
Filippo Crimì Emilio Quaia Giulio Cabrelle Chiara Zanon Alessia Pepe Daniela Regazzo Irene Tizianel Carla Scaroni Filippo Ceccato 《International journal of molecular sciences》2022,23(2)
Adrenal incidentalomas (AIs) are incidentally discovered adrenal neoplasms. Overt endocrine secretion (glucocorticoids, mineralocorticoids, and catecholamines) and malignancy (primary or metastatic disease) are assessed at baseline evaluation. Size, lipid content, and washout characterise benign AIs (respectively, <4 cm, <10 Hounsfield unit, and rapid release); nonetheless, 30% of adrenal lesions are not correctly indicated. Recently, image-based texture analysis from computed tomography (CT) may be useful to assess the behaviour of indeterminate adrenal lesions. We performed a systematic review to provide the state-of-the-art of texture analysis in patients with AI. We considered 9 papers (from 70 selected), with a median of 125 patients (range 20–356). Histological confirmation was the most used criteria to differentiate benign from the malignant adrenal mass. Unenhanced or contrast-enhanced data were available in all papers; TexRAD and PyRadiomics were the most used software. Four papers analysed the whole volume, and five considered a region of interest. Different texture features were reported, considering first- and second-order statistics. The pooled median area under the ROC curve in all studies was 0.85, depicting a high diagnostic accuracy, up to 93% in differentiating adrenal adenoma from adrenocortical carcinomas. Despite heterogeneous methodology, texture analysis is a promising diagnostic tool in the first assessment of patients with adrenal lesions. 相似文献
39.
Martina Magni Chiara Paolizzi Chiara Monfrini Cristina Vella Paolo Corradini Cristiana Carniti 《International journal of molecular sciences》2022,23(7)
Mature T-cell lymphomas (MTCLs) represent a heterogeneous group of aggressive non-Hodgkin lymphomas comprising different entities. Anthracycline-based regimens are considered the standard of care in the front-line treatment. However, responses to these approaches have been neither adequate nor durable, and new treatment strategies are urgently needed to improve survival. Genomic instability is a common feature of cancer cells and can be caused by aberrations in the DNA damage response (DDR) and DNA repair mechanisms. Consistently, molecules involved in DDR are being targeted to successfully sensitize cancer cells to chemotherapy. Recent studies showed that some hematological malignancies display constitutive DNA damage and intrinsic DDR activation, but these features have not been investigated yet in MTCLs. In this study, we employed a panel of malignant T cell lines, and we report for the first time the characterization of intrinsic DNA damage and basal DDR activation in preclinical models in T-cell lymphoma. Moreover, we report the efficacy of targeting the apical kinase ATM using the inhibitor AZD0156, in combination with standard chemotherapy to promote apoptotic cell death. These findings suggest that DDR is an attractive pathway to be pharmacologically targeted when developing novel therapies and improving MTCL patients’ outcomes. 相似文献
40.
Chiara Paolini Silvia Agarbati Devis Benfaremo Matteo Mozzicafreddo Silvia Svegliati Gianluca Moroncini 《International journal of molecular sciences》2022,23(7)
Systemic sclerosis (SSc) is a clinically heterogeneous disorder of the connective tissue characterized by vascular alterations, immune/inflammatory manifestations, and organ fibrosis. SSc pathogenesis is complex and still poorly understood. Therefore, effective therapies are lacking and remain nonspecific and limited to disease symptoms. In the last few years, many molecular and cellular mediators of SSc fibrosis have been described, providing new potential options for targeted therapies. In this review: (i) we focused on the PDGF/PDGFR pathway as key signaling molecules in the development of tissue fibrosis; (ii) we highlighted the possible role of stimulatory anti-PDGFRα autoantibodies in the pathogenesis of SSc; (iii) we reported the most promising PDGF/PDGFR targeting therapies. 相似文献