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排序方式: 共有995条查询结果,搜索用时 15 毫秒
41.
丙型病毒性肝炎(viral hepatitis type C,HC),系丙型肝炎病毒(HCV)感染所引起的疾病,HCV感染影响着全世界近2亿人群,是引起慢性肝脏疾病的主要病因,进一步会引起肝硬化、肝癌和肝功能衰竭。本文主要介绍HCV及其结构、基于不同靶点的治疗丙肝的药物(标准方案、DAA药物、DAA药物联合标准方案、DAA药物相联合、其他药物联合、HCV疫苗等)的最新研发动态,并对目前的研发现状进行了展望。 相似文献
42.
Cosmin Stefan Mocanu Marius Niculaua Gheorghita Zbancioc Violeta Mangalagiu Gabi Drochioiu 《International journal of molecular sciences》2022,23(5)
Our work discusses the investigation of 75 peptide-based drugs with the potential ability to break the β-sheet structures of amyloid-beta peptides from senile plaques. Hence, this study offers a unique insight into the design of neuropeptide-based drugs with β-sheet breaker potential in the amyloid-beta cascade for Alzheimer’s disease (AD). We started with five peptides (15QKLVFF20, 16KLVFF20, 17LVFF20, 16KLVF19 and 15QKLV18), to which 14 different organic acids were attached at the N-terminal. It was necessary to evaluate the physiochemical features of these sequences due to the biological correlation with our proposal. Hence, the preliminary analysis of different pharmacological features provided the necessary data to select the peptides with the best biocompatibility for administration purposes. Our approaches demonstrated that the peptides 17LVFF20, NA-17LVFF20, 16KLVF19 and NA-16KLVF19 (NA-nicotinic acid) have the ability to interfere with fibril formation and hence improve the neuro and cognitive functions. Moreover, the peptide conjugate NA-16KLVF19 possesses attractive pharmacological properties, demonstrated by in silico and in vitro studies. Tandem mass spectrometry showed no fragmentation for the spectra of 16KLVF19. Such important results suggest that under the action of protease, the peptide cleavage does not occur at all. Additionally, circular dichroism confirmed docking simulations and showed that NA-16KLVF19 may improve the β-sheet breaker mechanism, and thus the entanglement process of amyloid-beta peptides can be more effective. 相似文献
43.
One of the strategies in the search for safe and effective analgesic drugs is the design of multitarget analgesics. Such compounds are intended to have high affinity and activity at more than one molecular target involved in pain modulation. In the present contribution we summarize the attempts in which fentanyl or its substructures were used as a μ-opioid receptor pharmacophoric fragment and a scaffold to which fragments related to non-opioid receptors were attached. The non-opioid ‘second’ targets included proteins as diverse as imidazoline I2 binding sites, CB1 cannabinoid receptor, NK1 tachykinin receptor, D2 dopamine receptor, cyclooxygenases, fatty acid amide hydrolase and monoacylglycerol lipase and σ1 receptor. Reviewing the individual attempts, we outline the chemistry, the obtained pharmacological properties and structure-activity relationships. Finally, we discuss the possible directions for future work. 相似文献
44.
Hala Skayneh Batoul Jishi Rita Hleihel Maguy Hamie Rana El Hajj Carine Deleuze-Masquefa Pierre-Antoine Bonnet Marwan El Sabban Hiba El Hajj 《International journal of molecular sciences》2022,23(7)
Nucleophosmin-1 (NPM1) is a pleiotropic protein involved in numerous cellular processes. NPM1 shuttles between the nucleus and the cytoplasm, but exhibits a predominant nucleolar localization, where its fate and functions are exquisitely controlled by dynamic post-translational modifications (PTM). Sentrin/SUMO Specific Peptidase 3 (SENP3) and ARF are two nucleolar proteins involved in NPM1 PTMs. SENP3 antagonizes ARF-mediated NPM1 SUMOylation, to promote ribosomal biogenesis. In Acute Myeloid Leukemia (AML), NPM1 is frequently mutated, and exhibits an aberrant cytoplasmic localization (NPM1c). NPM1c mutations define a separate AML entity with good prognosis in some AML patients, rendering NPM1c as a potential therapeutic target. SENP3-mediated NPM1 de-SUMOylation induces resistance to therapy in NPM1c AML. Here, we demonstrate that the imidazoquinoxaline EAPB0503 prolongs the survival and results in selective reduction in the leukemia burden of NPM1c AML xenograft mice. Indeed, EAPB0503 selectively downregulates HDM2 expression and activates the p53 pathway in NPM1c expressing cells, resulting in apoptosis. Importantly, we unraveled that NPM1c expressing cells exhibit low basal levels of SUMOylation paralleled with high SENP3 and low ARF basal levels. EAPB0503 reverted these molecular players by inducing NPM1c SUMOylation and ubiquitylation, leading to its proteasomal degradation. EAPB0503-induced NPM1c SUMOylation is concurrent with SENP3 downregulation and ARF upregulation in NPM1c expressing cells. Collectively, these results provide a strong rationale for testing therapies modulating NPM1c post-translational modifications in the management of NPM1c AML. 相似文献
45.
Joanna Sikora Aleksandra Karczmarska-Wdzka Joanna Bugieda Przemysaw Sobczak 《International journal of molecular sciences》2022,23(3)
Ischemic stroke is a disease related to abnormal blood flow that leads to brain dysfunction. The early and late phases of the disease are distinguished. A distinction is made between the early and late stages of the disease, and the best effect in treating an ischemic stroke is usually achieved within the first hours after the onset of symptoms. This review looked at studies platelet activity monitoring studies to determine the risks and benefits of various approaches including antiplatelet therapy. A study was conducted on recently published literature based on PRISMA. This review includes 32 research articles directly addressing the importance of monitoring platelet function during antiplatelet therapy (dual or monotherapy) after ischemic stroke. In patients with transient ischemic attack or ischemic stroke, antiplatelet therapy can reduce the risk of stroke by 11–15%, assuming that patients respond well. Secondary prevention results are dependent on platelet reactivity, meaning that patients do not respond equally to antiplatelet therapy. It is very important that aspirin-resistant patients can benefit from the use of dual antiplatelet therapy. The individualized approach to secondary stroke prevention is to administer the most appropriate drug at the correct dose and apply the optimal therapeutic procedure to the individual patient. 相似文献
46.
Poly(ε-caprolactone) (PCL) is a bioresorbable and biocompatible polymer with assorted medical applications. However, remarkable hydrophobicity and nonosteoconductivity have stood as a barrier to limit its applications. The present study aims to modify the bulk characteristics of PCL to develop a polymeric scaffold with adequate structural and mechanical properties to support regenerated tissues. For this purpose, functionalized bacterial cellulose nanowhiskers (BCNW-g-βCD-PCL2000) are synthesized. Reinforcing PCL matrix with 4 wt % of the nanowhiskers resulted in a bionanocomposite with promoted bulk properties. Compared to neat PCL, the obtained bionanocomposite shows improvements of 115 and 51% in tensile strength and Young's modulus, respectively; 20% increase in hydrophilicity; 7% increase in degradation rate; and 6% decrease in crystallinity. Gas foaming/combined particulate leaching technique is used to develop highly porous structures of 86–95% porosity with interconnected macropores of mean pore diameters of 250–420 μm. Porous scaffolds showed compression modulus values of 5.3–9.1 MPa and would have promising applications in regenerative medicine. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48481. 相似文献
47.
48.
建立了一种微波消解-电感耦合等离子体质谱法(ICP-MS)测定利奥西呱原料药中残留钯含量的方法。方法:对样品进行微波消解前处理,优化调谐仪器参数后,以相对稳定的铑(1 03 Rh)作在线内标校准,采用ICP-MS法对样品中的钯元素进行定量测定分析。结果表明,原料药中钯元素标准曲线的线性范围为0~60.0μg/L,相关系数r为0.9996;7次重复性测试的相对标准偏差RSD为0.85%;加标回收率为90.14%~101.3%,相对标准偏差RSD为2.17%~2.44%。表明该方法简便快速、灵敏度高,准确可靠,适用于利奥西呱原料药中残留钯含量的测定。 相似文献
49.
Illicit drug consumption estimations derived from wastewater analysis: A critical review 总被引:1,自引:0,他引:1
Alexander L.N. van NuijsSara Castiglioni Isabela TarcomnicuCristina Postigo Miren Lopez de AldaHugo Neels Ettore ZuccatoDamia Barcelo Adrian Covaci 《The Science of the total environment》2011,409(19):3564-3577
The consumption of illicit drugs causes indisputable societal and economic damage. Therefore it is necessary to know their usage levels and trends for undertaking targeted actions to reduce their use. Recently, a new approach (namely sewage epidemiology) was developed for the estimation of illicit drug use based on measurements of urinary excreted illicit drugs and their metabolites in untreated wastewater. This review aims at critically evaluating the published literature and identifying research gaps of sewage epidemiology. Firstly, the existing analytical procedures for the determination of the four most used classes of illicit drugs worldwide (cannabis, cocaine, opiates and amphetamine-like stimulants) and their metabolites in wastewater are summarized and discussed. The focus lies on the sample preparation and on the analysis with chromatographic techniques coupled to mass spectrometry. Secondly, back-calculations used to transform measured concentrations in wastewater (in ng/L) into an amount of used illicit drug (in g/day per 1000 inhabitants or doses/day per 1000 inhabitants) are discussed in detail for the four groups of illicit drugs. Sewage epidemiology data from Spain, Belgium, UK, Italy, Switzerland and USA are summarized and compared with data from international organisations, such as the European Monitoring Centre for Drug and Drug Addiction (EMCDDA) and the United Nations Office on Drugs and Crime (UNODC). The results derived from wastewater analysis show in general good agreement with existing prevalence data (percentage of a population that uses illicit drugs at a given time) and demonstrate the potential of sewage epidemiology. However, this review confirms that future work should focus on further optimisation and standardisation of various important parameters (e.g. sample collection and back-calculations). In the future, sewage epidemiology could be used in routine drug monitoring campaigns as a valuable tool in addition to the classical socio-epidemiological studies for the determination of local, national and international illicit drug use. 相似文献
50.