全文获取类型
收费全文 | 1608篇 |
免费 | 54篇 |
国内免费 | 37篇 |
专业分类
电工技术 | 31篇 |
综合类 | 56篇 |
化学工业 | 334篇 |
金属工艺 | 43篇 |
机械仪表 | 47篇 |
建筑科学 | 43篇 |
矿业工程 | 8篇 |
能源动力 | 45篇 |
轻工业 | 116篇 |
水利工程 | 17篇 |
石油天然气 | 8篇 |
武器工业 | 1篇 |
无线电 | 130篇 |
一般工业技术 | 212篇 |
冶金工业 | 355篇 |
原子能技术 | 28篇 |
自动化技术 | 225篇 |
出版年
2023年 | 8篇 |
2022年 | 60篇 |
2021年 | 56篇 |
2020年 | 19篇 |
2019年 | 24篇 |
2018年 | 21篇 |
2017年 | 24篇 |
2016年 | 32篇 |
2015年 | 28篇 |
2014年 | 24篇 |
2013年 | 78篇 |
2012年 | 52篇 |
2011年 | 75篇 |
2010年 | 58篇 |
2009年 | 45篇 |
2008年 | 58篇 |
2007年 | 59篇 |
2006年 | 44篇 |
2005年 | 46篇 |
2004年 | 36篇 |
2003年 | 53篇 |
2002年 | 80篇 |
2001年 | 88篇 |
2000年 | 61篇 |
1999年 | 46篇 |
1998年 | 105篇 |
1997年 | 74篇 |
1996年 | 49篇 |
1995年 | 35篇 |
1994年 | 22篇 |
1993年 | 30篇 |
1992年 | 14篇 |
1991年 | 14篇 |
1990年 | 9篇 |
1989年 | 16篇 |
1988年 | 12篇 |
1987年 | 6篇 |
1986年 | 16篇 |
1985年 | 18篇 |
1984年 | 7篇 |
1983年 | 14篇 |
1982年 | 7篇 |
1981年 | 8篇 |
1980年 | 9篇 |
1979年 | 5篇 |
1978年 | 10篇 |
1977年 | 9篇 |
1976年 | 9篇 |
1971年 | 3篇 |
1966年 | 3篇 |
排序方式: 共有1699条查询结果,搜索用时 281 毫秒
71.
Valentina Tedeschi Giorgia Paldino Martina Kunkl Marino Paroli Rosa Sorrentino Loretta Tuosto Maria Teresa Fiorillo 《International journal of molecular sciences》2022,23(6)
CD8+ T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, they turn into memory lymphocytes, thus providing a long-term protection. During ageing, the thymic involution causes a reduction of circulating T cells and an enrichment of memory cells, partially explaining the lowering of the response towards novel antigens with implications in vaccine efficacy. Moreover, the persistent stimulation by several antigens throughout life favors the switching of CD8+ T cells towards a senescent phenotype contributing to a low-grade inflammation that is a major component of several ageing-related diseases. In genetically predisposed young people, an immunological stress caused by viral infections (e.g., HIV, CMV, SARS-CoV-2), autoimmune disorders or tumor microenvironment (TME) could mimic the ageing status with the consequent acceleration of T cell senescence. This, in turn, exacerbates the inflamed conditions with dramatic effects on the clinical progression of the disease. A better characterization of the phenotype as well as the functions of senescent CD8+ T cells can be pivotal to prevent age-related diseases, to improve vaccine strategies and, possibly, immunotherapies in autoimmune diseases and cancer. 相似文献
72.
Dra Szab Zsolt Srszegi Beta Polgr va Sghy Dra Regldi Tünde Tth Zsfia Ondi Przemyslaw Leszek Zoltn V. Varga Zsuzsanna Helyes gnes Kemny Pter Ferdinandy Andrea Tams 《International journal of molecular sciences》2022,23(7)
Pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) is a multifunctional neuropeptide, which may play a role in cardioprotection. However, little is known about the presence of PACAP-38 in heart failure (HF) patients. The aim of our study was to measure the alterations of PACAP-38 like immunoreactivity (LI) in acute (n = 13) and chronic HF (n = 33) and to examine potential correlations between PACAP-38 and HF predictors (cytokines, NT-proBNP). Tissue PACAP-38 LI and PAC1 receptor levels were also investigated in heart tissue samples of patients with HF. Significantly higher plasma PACAP-38 LI was detected in patients with acute HF, while in chronic HF patients, a lower level of immunoreactivity was observed compared to healthy controls (n = 13). Strong negative correlation was identified between plasma PACAP-38 and NT-proBNP levels in chronic HF, as opposed to the positive connection seen in the acute HF group. Plasma IL-1 β, IL-2 and IL-4 levels were significantly lower in chronic HF, and IL-10 was significantly higher in patients with acute HF. PACAP-38 levels of myocardial tissues were lower in all end-stage HF patients and lower PAC1 receptor levels were detected in the primary dilated cardiomyopathy group compared to the controls. We conclude that PACAP-38 and PAC1 expression correlates with some biomarkers of acute and chronic HF; therefore, further studies are necessary to explore whether PACAP could be a suitable prognostic biomarker in HF patients. 相似文献
73.
Bianka Vrnai Ferenc Zsila Zoltn Szakcs Zsfia Gardi Milo Malanga Szabolcs Bni 《International journal of molecular sciences》2022,23(7)
Mitragynine (MTR), the main indole alkaloid of the well-known plant kratom (Mitragyna speciosa), is one of the most studied natural products nowadays, due to its remarkable biological effects. It is a partial agonist on the opioid receptors, and as such relieves pain without the well-known side-effects of the opioids applied in the clinical practice. MTR and its derivatives therefore became novel candidates for drug development. The poor aqueous solubility and low bioavailability of drugs are often improved by cyclodextrins (CyDs) as excipients through host-guest type complex formation. Among the wide variety of CyDs, sulfobutylether-beta-cyclodextrin (SBEβCyD) is frequently used and official in the European and U.S. Pharmacopoeia. Herein, the host-guest complexation of MTR with βCyD and SBEβCyD was studied using chiroptical and NMR spectroscopy. It was found by NMR measurements that MTR forms a rather weak (logβ11 = 0.8) 1:1 host-guest complex with βCyD, while the co-existence of the 2MTR∙SBEβCyD and MTR∙SBEβCyD species was deducted from 1H NMR titrations in the millimolar MTR concentration range. Sulfobutylation of βCyD significantly enhanced the affinity towards MTR. The structure of the formed inclusion complex was extensively studied by circular dichroism spectroscopy and 2D ROESY NMR. The insertion of the indole moiety was confirmed by both techniques. 相似文献
74.
Davide Loizzo Savio Domenico Pandolfo Devin Rogers Clara Cerrato Nicola Antonio di Meo Riccardo Autorino Vincenzo Mirone Matteo Ferro Camillo Porta Alessandro Stella Cinzia Bizzoca Leonardo Vincenti Marco Spilotros Monica Rutigliano Michele Battaglia Pasquale Ditonno Giuseppe Lucarelli 《International journal of molecular sciences》2022,23(7)
Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible. 相似文献
75.
Maria Rosaria di Nunzio Mario Gutirrez Jos María Moreno Avelino Corma Urbano Díaz Abderrazzak Douhal 《International journal of molecular sciences》2022,23(1)
In this contribution, we report on the solid-state-photodynamical properties and further applications of a low dimensional composite material composed by the luminescent trans-4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCM) dye interacting with a two-dimensional-metal organic framework (2D-MOF), Al-ITQ-HB. Three different samples with increasing concentration of DCM are synthesized and characterized. The broad UV-visible absorption spectra of the DCM/Al-ITQ-HB composites reflect the presence of different species of DCM molecules (monomers and aggregates). In contrast, the emission spectra are narrower and exhibit a bathochromic shift upon increasing the DCM concentration, in agreeance with the formation of adsorbed aggregates. Time-resolved picosecond (ps)-experiments reveal multi-exponential behaviors of the excited composites, further confirming the heterogeneous nature of the samples. Remarkably, DCM/Al-ITQ-HB fluorescence is sensitive to vapors of electron donor aromatic amine compounds like aniline, methylaniline, and benzylamine due to a H-bonding-induced electron transfer (ET) process from the analyte to the surface-adsorbed DCM. These findings bring new insights on the photobehavior of a well-known dye when interacting with a 2D-MOF and its possible application in sensing aniline derivatives. 相似文献
76.
Federica Barbagallo Sandro La Vignera Rossella Cannarella Laura M. Mongioì Vincenzo Garofalo Claudia Leanza Marta Marino Aldo E. Calogero Rosita A. Condorelli 《International journal of molecular sciences》2022,23(2)
Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years. 相似文献
77.
β-Cyclodextrin (β-CD) has been applied in various fields of drug formulation. Its presence in powder Paracetamol (PAR) products prepared with different methods (kneading and spray drying) changes the morphology of original drug. The product made by spray drying has nearly isodimensional spherical particles, and potentially better flowability than the kneaded product. Spray drying of PAR product without β-CD shows similar morphology like a product with β-CD, but the particles show a greater inclination to adhesion. The results were obtained by electron microscopic study. 相似文献
78.
Judit Olh Tibor Sznsi Attila Lehotzky Victor Norris Judit Ovdi 《International journal of molecular sciences》2022,23(3)
Protein–protein interactions (PPIs) outnumber proteins and are crucial to many fundamental processes; in consequence, PPIs are associated with several pathological conditions including neurodegeneration and modulating them by drugs constitutes a potentially major class of therapy. Classically, however, the discovery of small molecules for use as drugs entails targeting individual proteins rather than targeting PPIs. This is largely because discovering small molecules to modulate PPIs has been seen as extremely challenging. Here, we review the difficulties and limitations of strategies to discover drugs that target PPIs directly or indirectly, taking as examples the disordered proteins involved in neurodegenerative diseases. 相似文献
79.
80.
Capt. Courtney Kiggins Austin Skinner Prof. Marino J. E. Resendiz 《Chembiochem : a European journal of chemical biology》2020,21(9):1347-1355
Aptamers are attractive constructs due to their high affinity/selectivity towards a target. Here 7,8-dihydro-8-oxoguanosine (8-oxoG) has been used, due in part to its unique H-bonding capabilities (Watson–Crick or Hoogsteen), to expand the “RNA alphabet”. Its impact on the theophylline RNA aptamer was explored by modifying its binding pocket at positions G11, G25, or G26. Structural probing, with RNases A and T1, showed that modification at G11 leads to a drastic structural change, whereas the G25-/G26-modified analogues exhibited cleavage patterns similar to that of the canonical construct. The recognition properties towards three xanthine derivatives were then explored through thermophoresis. Modifying the aptamer at position G11 led to binding inhibition. Modification at G25, however, changed the selectivity towards theobromine (Kd≈160 μm ), with a poor affinity for theophylline (Kd>1.5 mm ) being observed. Overall, 8-oxoG can have an impact on the structures of aptamers in a position-dependent manner, leading to altered target selectivity. 相似文献