全文获取类型
收费全文 | 7160篇 |
免费 | 547篇 |
国内免费 | 5篇 |
专业分类
电工技术 | 23篇 |
综合类 | 1篇 |
化学工业 | 2546篇 |
金属工艺 | 48篇 |
机械仪表 | 128篇 |
建筑科学 | 265篇 |
矿业工程 | 11篇 |
能源动力 | 177篇 |
轻工业 | 2444篇 |
水利工程 | 63篇 |
石油天然气 | 52篇 |
无线电 | 224篇 |
一般工业技术 | 843篇 |
冶金工业 | 179篇 |
原子能技术 | 19篇 |
自动化技术 | 689篇 |
出版年
2024年 | 18篇 |
2023年 | 120篇 |
2022年 | 418篇 |
2021年 | 467篇 |
2020年 | 262篇 |
2019年 | 277篇 |
2018年 | 304篇 |
2017年 | 272篇 |
2016年 | 340篇 |
2015年 | 250篇 |
2014年 | 377篇 |
2013年 | 568篇 |
2012年 | 533篇 |
2011年 | 556篇 |
2010年 | 413篇 |
2009年 | 414篇 |
2008年 | 382篇 |
2007年 | 337篇 |
2006年 | 241篇 |
2005年 | 208篇 |
2004年 | 152篇 |
2003年 | 125篇 |
2002年 | 127篇 |
2001年 | 71篇 |
2000年 | 71篇 |
1999年 | 73篇 |
1998年 | 54篇 |
1997年 | 38篇 |
1996年 | 35篇 |
1995年 | 31篇 |
1994年 | 26篇 |
1993年 | 19篇 |
1992年 | 19篇 |
1991年 | 9篇 |
1990年 | 6篇 |
1989年 | 26篇 |
1988年 | 11篇 |
1987年 | 17篇 |
1986年 | 6篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 2篇 |
1982年 | 7篇 |
1981年 | 1篇 |
1980年 | 4篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1964年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有7712条查询结果,搜索用时 0 毫秒
101.
The fact that Z is a specification language only, with no associated program development method, is a widely recognised problem.
As an answer to that, we present ZRC, a refinement calculus based on Morgan's work that incorporates the Z notation and follows
its style and conventions. This work builds upon existing refinement techniques for Z, but distinguishes itself mainly in
that ZRC is completely formalised. In this paper, we explain how programs can be derived from Z specifications using ZRC.
We present ZRC-L, the language of our calculus, and its conversion laws, which are concerned with the transformation of Z
schemas into programs of this language. Moreover, we present the weakest precondition semantics of ZRC-L, which is the basis
for the derivation of the laws of ZRC. More than a refinement calculus, ZRC is a theory of refinement for Z.
Received July 1997 / Accepted in revised form October 1998 相似文献
102.
Ana Sofia Ferreira Ana Margarida Silva Diana Pinto Manuela M. Moreira Ricardo Ferraz Jaroslava varc-Gaji Paulo C. Costa Cristina Delerue-Matos Francisca Rodrigues 《International journal of molecular sciences》2022,23(23)
Oral mucositis (OM), a common side effect of oncological treatment, is an oral mucosal disorder characterized by painful ulcerations and increased risk of infection. The use of natural antioxidants to suppress the redox imbalance responsible for the OM condition has emerged as an interesting approach to prevent/treat OM. This study aims to explore the chestnut (Castana sativa) shells as potential active ingredient against OM. Therefore, chestnut shells were extracted at different temperatures (110–180 °C) by Subcritical Water Extraction (SWE), aiming to recover antioxidants. The extracts were also evaluated against microorganisms present in the oral cavity as well as on human oral cell lines (TR146 and HSC3). The highest phenolic content was obtained with the extraction temperature of 110 °C, exhibiting the best antioxidant/antiradical activities and scavenging efficiencies against HOCl (IC50 = 4.47 μg/mL) and ROO• (0.73 μmol TE/mg DW). High concentrations of phenolic acids (e.g., gallic and protocatechuic acids) and flavanoids (catechin, epicatechin and rutin) characterized the phenolic profile. The antimicrobial activity against several oral microorganisms present in the oral cavity during OM, such as Streptococcus, Staphylococcus, Enterococcus, and Escherichia, was demonstrated. Finally, the effects on HSC3 and TR146 cell lines revealed that the extract prepared at 110 °C had the lowest IC50 (1325.03 and 468.15 µg/mL, respectively). This study highlights the potential effects of chestnut shells on OM. 相似文献
103.
Leonel Pekarek Basilio De la Torre-Escuredo Oscar Fraile-Martinez Cielo García-Montero Miguel A. Saez David Cobo-Prieto Luis G. Guijarro Jose V. Saz Patricia De Castro-Martinez Diego Torres-Carranza Tatiana Pekarek Ana Clara Carrera Melchor Alvarez-Mon Miguel A. Ortega 《International journal of molecular sciences》2022,23(23)
Osteosarcoma represents a rare cause of cancer in the general population, accounting for <1% of malignant neoplasms globally. Nonetheless, it represents the main cause of malignant bone neoplasm in children, adolescents and young adults under 20 years of age. It also presents another peak of incidence in people over 50 years of age and is associated with rheumatic diseases. Numerous environmental risk factors, such as bone diseases, genetics and a history of previous neoplasms, have been widely described in the literature, which allows monitoring a certain group of patients. Diagnosis requires numerous imaging tests that make it possible to stratify both the local involvement of the disease and its distant spread, which ominously determines the prognosis. Thanks to various clinical trials, the usefulness of different chemotherapy regimens, radiotherapy and surgical techniques with radical intent has now been demonstrated; these represent improvements in both prognosis and therapeutic approaches. Osteosarcoma patients should be evaluated in reference centres by multidisciplinary committees with extensive experience in proper management. Although numerous genetic and rheumatological diseases and risk factors have been described, the use of serological, genetic or other biomarkers has been limited in clinical practice compared to other neoplasms. This limits both the initial follow-up of these patients and screening in populations at risk. In addition, we cannot forget that the diagnosis is mainly based on the direct biopsy of the lesion and imaging tests, which illustrates the need to study new diagnostic alternatives. Therefore, the purpose of this study is to review the natural history of the disease and describe the main biomarkers, explaining their clinical uses, prognosis and limitations. 相似文献
104.
Ines Maestro Laura R. de la Ballina Gracia Porras Silvia Corrochano Eva De Lago Anne Simonsen Patricia Boya Ana Martinez 《International journal of molecular sciences》2022,23(20)
Mitophagy is the selective degradation of mitochondria by autophagy. It promotes the turnover of mitochondria and prevents the accumulation of dysfunctional mitochondria, which can lead to cellular degeneration. Mitophagy is known to be altered in several pathological conditions, especially in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We recently demonstrated an increase in autophagy flux in lymphoblasts from ALS patients bearing a mutation in SOD1. Thus, the identification of mitophagy inhibitors may be a therapeutic option to recover mitochondrial homeostasis. Here, using a phenotypic mitophagy assay, we identified a new mitophagy inhibitor, the small molecule named IGS2.7 from the MBC library. Interestingly, the treatment of different cellular and in vivo models of ALS with mutations on SOD1 and TARDBP with this inhibitor restores autophagy to control levels. These results point mitophagy inhibitors, especially IGS2.7, to a new therapeutic approach for familial ALS patients. 相似文献
105.
Rosa Luisa Ambrosio Catalina Ana Rossell Doralicia Casares Gianna Palmieri Aniello Anastasio Pablo V. Escrib 《International journal of molecular sciences》2022,23(20)
Since penicillin was discovered, antibiotics have been critical in the fight against infections. However, antibiotic misuse has led to drug resistance, which now constitutes a serious health problem. In this context, antimicrobial peptides (AMPs) constitute a natural group of short proteins, varying in structure and length, that act against certain types of bacterial pathogens. The antimicrobial peptide 1018-K6 (VRLIVKVRIWRR- NH2) has significant bactericidal and antibiofilm activity against Listeria monocytogenes isolates, and against different strains and serotypes of Salmonella. Here, the mechanism of action of 1018-K6 was explored further to understand the peptide–membrane interactions relevant to its activity, and to define their determinants. We combined studies with model synthetic membranes (liposomes) and model biological membranes, assessing the absorption maximum and the quenching of 1018-K6 fluorescence in aqueous and lipid environments, the self-quenching of carboxyfluorescein, as well as performing lipid sedimentation assays. The data obtained reflect the differential interactions of the 1018-K6 peptide with eukaryotic and prokaryotic membranes, and the specific interactions and mechanisms of action in the three prokaryotic species studied: Salmonella Typhimurium2GN, Escherichia coli3GN, and Staphylococcus aureus3GP. The AMP 1018-K6 is a candidate to prevent (food preservation) or treat (antibiotic use) infections caused by certain pathogenic bacteria, especially some that are resistant to current antibiotics. 相似文献
106.
Ana Patrícia Simes Francisco Q. Gonalves Daniel Rial Samira G. Ferreira Joo Pedro Lopes Paula M. Canas Rodrigo A. Cunha 《International journal of molecular sciences》2022,23(21)
Adenosine A2A receptors (A2AR) control fear memory and the underlying processes of synaptic plasticity in the amygdala. In other brain regions, A2AR activation is ensured by ATP-derived extracellular adenosine formed by ecto-5′-nucleotidase or CD73. We now tested whether CD73 is also responsible to provide for the activation of A2AR in controlling fear memory and amygdala long-term potentiation (LTP). The bilateral intracerebroventricular injection of the CD73 inhibitor αβ-methylene ADP (AOPCP, 1 nmol/ventricle/day) phenocopied the effect of the A2AR blockade by decreasing the expression of fear memory, an effect disappearing in CD73-knockout (KO) mice and in forebrain neuronal A2AR-KO mice. In the presence of PPADS (20 μM) to eliminate any modification of ATP/ADP-mediated P2 receptor effects, both AOPCP (100 μM) and the A2AR antagonist, (50 nM), decreased LTP magnitude in synapses of projection from the external capsula into the lateral amygdala, an effect eliminated in slices from both forebrain neuronal A2AR-KO mice and CD73-KO mice. These data indicate a key role of CD73 in the process of A2AR-mediated control of fear memory and underlying synaptic plasticity processes in the amygdala, paving the way to envisage CD73 as a new therapeutic target to interfere with abnormal fear-like emotional processing. SCH58261相似文献
107.
Catarina M. Morais Ana M. Cardoso Ana Rita D. Araújo Ana Reis Pedro Domingues Maria Rosrio M. Domingues Maria C. Pedroso de Lima Amlia S. Jurado 《International journal of molecular sciences》2022,23(21)
Modulation of lipid metabolism is a well-established cancer hallmark, and SCD1 has been recognized as a key enzyme in promoting cancer cell growth, including in glioblastoma (GBM), the deadliest brain tumor and a paradigm of cancer resistance. The central goal of this work was to identify, by MS, the phospholipidome alterations resulting from the silencing of SCD1 in human GBM cells, in order to implement an innovative therapy to fight GBM cell resistance. With this purpose, RNAi technology was employed, and low serum-containing medium was used to mimic nutrient deficiency conditions, at which SCD1 is overexpressed. Besides the expected increase in the saturated to unsaturated fatty acid ratio in SCD1 silenced-GBM cells, a striking increase in polyunsaturated chains, particularly in phosphatidylethanolamine and cardiolipin species, was noticed and tentatively correlated with an increase in autophagy (evidenced by the increase in LC3BII/I ratio). The contribution of autophagy to mitigate the impact of SCD1 silencing on GBM cell viability and growth, whose modest inhibition could be correlated with the maintenance of energetically associated mitochondria, was evidenced by using autophagy inhibitors. In conclusion, SCD1 silencing could constitute an important tool to halt GBM resistance to the available treatments, especially when coupled with a mitochondria disrupter chemotherapeutic. 相似文献
108.
Diana Loureno Raquel Lopes Carolina Pestana Ana C. Queirs Cristina Joo Emilie Arnault Carneiro 《International journal of molecular sciences》2022,23(21)
Despite the wide variety of existing therapies, multiple myeloma (MM) remains a disease with dismal prognosis. Choosing the right treatment for each patient remains one of the major challenges. A new approach being explored is the use of ex vivo models for personalized medicine. Two-dimensional culture or animal models often fail to predict clinical outcomes. Three-dimensional ex vivo models using patients’ bone marrow (BM) cells may better reproduce the complexity and heterogeneity of the BM microenvironment. Here, we review the strengths and limitations of currently existing patient-derived ex vivo three-dimensional MM models. We analyze their biochemical and biophysical properties, molecular and cellular characteristics, as well as their potential for drug testing and identification of disease biomarkers. Furthermore, we discuss the remaining challenges and give some insight on how to achieve a more biomimetic and accurate MM BM model. Overall, there is still a need for standardized culture methods and refined readout techniques. Including both myeloma and other cells of the BM microenvironment in a simple and reproducible three-dimensional scaffold is the key to faithfully mapping and examining the relationship between these players in MM. This will allow a patient-personalized profile, providing a powerful tool for clinical and research applications. 相似文献
109.
110.
Joel Gruchot Ferdinand Lein Isabel Lewen Laura Reiche Vivien Weyers Patrick Petzsch Peter Gttle Karl Khrer Hans-Peter Hartung Patrick Küry David Kremer 《International journal of molecular sciences》2022,23(21)
Siponimod (Mayzent®), a sphingosine 1-phosphate receptor (S1PR) modulator which prevents lymphocyte egress from lymphoid tissues, is approved for the treatment of relapsing-remitting and active secondary progressive multiple sclerosis. It can cross the blood–brain barrier (BBB) and selectively binds to S1PR1 and S1PR5 expressed by several cell populations of the central nervous system (CNS) including microglia. In multiple sclerosis, microglia are a key CNS cell population moving back and forth in a continuum of beneficial and deleterious states. On the one hand, they can contribute to neurorepair by clearing myelin debris, which is a prerequisite for remyelination and neuroprotection. On the other hand, they also participate in autoimmune inflammation and axonal degeneration by producing pro-inflammatory cytokines and molecules. In this study, we demonstrate that siponimod can modulate the microglial reaction to lipopolysaccharide-induced pro-inflammatory activation. 相似文献