全文获取类型
收费全文 | 4246篇 |
免费 | 236篇 |
国内免费 | 16篇 |
专业分类
化学 | 3516篇 |
晶体学 | 18篇 |
力学 | 67篇 |
数学 | 431篇 |
物理学 | 466篇 |
出版年
2023年 | 50篇 |
2022年 | 141篇 |
2021年 | 178篇 |
2020年 | 142篇 |
2019年 | 120篇 |
2018年 | 60篇 |
2017年 | 57篇 |
2016年 | 178篇 |
2015年 | 180篇 |
2014年 | 163篇 |
2013年 | 241篇 |
2012年 | 340篇 |
2011年 | 379篇 |
2010年 | 213篇 |
2009年 | 176篇 |
2008年 | 294篇 |
2007年 | 259篇 |
2006年 | 254篇 |
2005年 | 181篇 |
2004年 | 190篇 |
2003年 | 150篇 |
2002年 | 126篇 |
2001年 | 28篇 |
2000年 | 32篇 |
1999年 | 26篇 |
1998年 | 20篇 |
1997年 | 21篇 |
1996年 | 25篇 |
1995年 | 20篇 |
1994年 | 17篇 |
1993年 | 8篇 |
1991年 | 7篇 |
1990年 | 6篇 |
1989年 | 10篇 |
1988年 | 5篇 |
1987年 | 8篇 |
1986年 | 10篇 |
1985年 | 21篇 |
1984年 | 21篇 |
1983年 | 17篇 |
1982年 | 19篇 |
1981年 | 19篇 |
1980年 | 11篇 |
1979年 | 9篇 |
1978年 | 7篇 |
1977年 | 13篇 |
1976年 | 8篇 |
1975年 | 8篇 |
1974年 | 7篇 |
1973年 | 5篇 |
排序方式: 共有4498条查询结果,搜索用时 15 毫秒
201.
Jessica Gasparello Chiara Papi Matteo Zurlo Laura Gambari Andrea Rozzi Alex Manicardi Roberto Corradini Roberto Gambari Alessia Finotti 《Molecules (Basel, Switzerland)》2022,27(4)
Glioblastoma multiforme (GBM) is a lethal malignant tumor accounting for 42% of the tumors of the central nervous system, the median survival being 15 months. At present, no curative treatment is available for GBM and new drugs and therapeutic protocols are urgently needed. In this context, combined therapy appears to be a very interesting approach. The isothiocyanate sulforaphane (SFN) has been previously shown to induce apoptosis and inhibit the growth and invasion of GBM cells. On the other hand, the microRNA miR-15b is involved in invasiveness and proliferation in GBM and its inhibition is associated with the induction of apoptosis. On the basis of these observations, the objective of the present study was to determine whether a combined treatment using SFN and a peptide nucleic acid interfering with miR-15b-5p (PNA-a15b) might be proposed for increasing the pro-apoptotic effects of the single agents. To verify this hypothesis, we have treated GMB U251 cells with SFN alone, PNA-a15b alone or their combination. The cell viability, apoptosis and combination index were, respectively, analyzed by calcein staining, annexin-V and caspase-3/7 assays, and RT-qPCR for genes involved in apoptosis. The efficacy of the PNA-a15b determined the miR-15b-5p content analyzed by RT-qPCR. The results obtained indicate that SFN and PNA-a15b synergistically act in inducing the apoptosis of U251 cells. Therefore, the PNA-a15b might be proposed in a “combo-therapy” associated with SFN. Overall, this study suggests the feasibility of using combined treatments based on PNAs targeting miRNA involved in GBM and nutraceuticals able to stimulate apoptosis. 相似文献
202.
Diana Trujillo-Benítez Myrna Luna-Gutirrez Guillermina Ferro-Flores Blanca Ocampo-García Clara Santos-Cuevas Gerardo Bravo-Villegas Enrique Morales-vila Pedro Cruz-Nova Lorenza Díaz-Nieto Janice García-Quiroz Erika Azorín-Vega Antonio Rosato Laura Melndez-Alafort 《Molecules (Basel, Switzerland)》2022,27(1)
Fibroblast activation protein (FAP) is expressed in the microenvironment of most human epithelial tumors. 68Ga-labeled FAP inhibitors based on the cyanopyrrolidine structure (FAPI) are currently used for the detection of the tumor microenvironment by PET imaging. This research aimed to design, synthesize and preclinically evaluate a new FAP inhibitor radiopharmaceutical based on the 99mTc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (99mTc-iFAP) structure for SPECT imaging. Molecular docking for affinity calculations was performed using the AutoDock software. The chemical synthesis was based on a series of coupling reactions of 6-hidrazinylnicotinic acid (HYNIC) and D-alanine to a boronic acid derivative. The iFAP was prepared as a lyophilized formulation based on EDDA/SnCl2 for labeling with 99mTc. The radiochemical purity (R.P.) was verified via ITLC-SG and reversed-phase radio-HPLC. The stability in human serum was evaluated by size-exclusion HPLC. In vitro cell uptake was assessed using N30 stromal endometrial cells (FAP positive) and human fibroblasts (FAP negative). Biodistribution and tumor uptake were determined in Hep-G2 tumor-bearing nude mice, from which images were acquired using a micro-SPECT/CT. The iFAP ligand (Ki = 0.536 nm, AutoDock affinity), characterized by UV-Vis, FT-IR, 1H–NMR and UPLC-mass spectroscopies, was synthesized with a chemical purity of 92%. The 99mTc-iFAP was obtained with a R.P. >98%. In vitro and in vivo studies indicated high radiotracer stability in human serum (>95% at 24 h), specific recognition for FAP, high tumor uptake (7.05 ± 1.13% ID/g at 30 min) and fast kidney elimination. The results found in this research justify additional dosimetric and clinical studies to establish the sensitivity and specificity of the 99mTc-iFAP. 相似文献
203.
204.
Christopher Hernandez Laura Cadenillas Cline Mathieu Jean-Denis Bailly Vanessa Durrieu 《Molecules (Basel, Switzerland)》2022,27(2)
Mimosa tenuiflora aqueous extract (MAE) is rich in phenolic compounds. Among them, condensed tannins have been demonstrated to exhibit a strong antioxidant and antiaflatoxin B1 activities in Aspergillus flavus. Since antioxidant capacity can change with time due to environmental interactions, this study aimed to evaluate the ability of encapsulation by spray-drying of Mimosa tenuiflora aqueous extract to preserve their biological activities through storage. A dry formulation may also facilitate transportation and uses. For that, three different wall materials were used and compared for their efficiency. Total phenolic content, antioxidant activity, antifungal and antiaflatoxin activities were measured after the production of the microparticles and after one year of storage at room temperature. These results confirmed that encapsulation by spray-drying using polysaccharide wall materials is able to preserve antiaflatoxin activity of Mimosa tenuiflora extract better than freezing. 相似文献
205.
206.
Laura Tblick Severien Van Keer Annemie De Smet Pierre Van Damme Michelle Laeremans Alejandra Rios Cortes Koen Beyers Vanessa Vankerckhoven Veerle Matheeussen Renee Mandersloot Arno Floore Chris J. L. M. Meijer Renske D. M. Steenbergen Alex Vorsters 《Molecules (Basel, Switzerland)》2021,26(7)
The potential of first-void (FV) urine as a non-invasive liquid biopsy for detection of human papillomavirus (HPV) DNA and other biomarkers has been increasingly recognized over the past decade. In this study, we investigated whether the volume of this initial urine stream has an impact on the analytical performance of biomarkers. In parallel, we evaluated different DNA extraction protocols and introduced an internal control in the urine preservative. Twenty-five women, diagnosed with high-risk HPV, provided three home-collected FV urine samples using three FV urine collection devices (Colli-Pee) with collector tubes that differ in volume (4, 10, 20 mL). Each collector tube was prefilled with Urine Conservation Medium spiked with phocine herpesvirus 1 (PhHV-1) DNA as internal control. Five different DNA extraction protocols were compared, followed by PCR for GAPDH and PhHV-1 (qPCR), HPV DNA, and HBB (HPV-Risk Assay), and ACTB (methylation-specific qPCR). Results showed limited effects of collection volume on human and HPV DNA endpoints. In contrast, significant variations in yield for human endpoints were observed for different DNA extraction methods (p < 0.05). Additionally, the potential of PhHV-1 as internal control to monitor FV urine collection, storage, and processing was demonstrated. 相似文献
207.
Saracino MA Mercolini L Musenga A Bugamelli F Raggi MA 《Journal of separation science》2008,31(10):1851-1859
Three analytical methods have been developed and compared for the quality control of a new formulation (Soymen GN(R) capsules) containing soy extract and melatonin for the treatment of menopausal symptoms. The first method is based on MEKC with diode-array detection, using a mixture of basic carbonate buffer (95%) and methanol (5%), containing 55 mM SDS, as the BGE. The second method is an HPLC method with UV detection at 260 nm. The third method is an HPLC method coupled to amperometric detection which is carried out at an oxidation potential of +0.8 V. In both HPLC systems, the chromatographic separation is obtained on an RP C18 column using a mixture of ACN and an acidic phosphate buffer (25:75 v/v) as the mobile phase. A feasible pretreatment procedure with a methanol/water mixture has been implemented to achieve the quantitative extraction of the main soy isoflavones and of melatonin from the capsules. The results obtained with the three methods are in good agreement with each other and satisfactory in terms of linearity (r(2) >0.9996), precision (RSD <5.4%) and accuracy (recovery >97%). Thus, each of the three analytical methods seems to be suitable for the simultaneous analysis of the main soy isoflavones and melatonin in the new commercial formulation. 相似文献
208.
209.
A truncated Newton method in an augmented Lagrangian framework for nonlinear programming 总被引:1,自引:0,他引:1
Gianni Di Pillo Giampaolo Liuzzi Stefano Lucidi Laura Palagi 《Computational Optimization and Applications》2010,45(2):311-352
In this paper we propose a primal-dual algorithm for the solution of general nonlinear programming problems. The core of the
method is a local algorithm which relies on a truncated procedure for the computation of a search direction, and is thus suitable
for large scale problems. The truncated direction produces a sequence of points which locally converges to a KKT pair with
superlinear convergence rate. 相似文献
210.
Egils Avots Klvs Jermakovs Maie Bachmann Laura Peske Cagri Ozcinar Gholamreza Anbarjafari 《Entropy (Basel, Switzerland)》2022,24(2)
Depression is a public health issue that severely affects one’s well being and can cause negative social and economic effects to society. To raise awareness of these problems, this research aims at determining whether the long-lasting effects of depression can be determined from electroencephalographic (EEG) signals. The article contains an accuracy comparison for SVM, LDA, NB, kNN, and D3 binary classifiers, which were trained using linear (relative band power, alpha power variability, spectral asymmetry index) and nonlinear (Higuchi fractal dimension, Lempel–Ziv complexity, detrended fluctuation analysis) EEG features. The age- and gender-matched dataset consisted of 10 healthy subjects and 10 subjects diagnosed with depression at some point in their lifetime. Most of the proposed feature selection and classifier combinations achieved accuracy in the range of 80% to 95%, and all the models were evaluated using a 10-fold cross-validation. The results showed that the motioned EEG features used in classifying ongoing depression also work for classifying the long-lasting effects of depression. 相似文献