全文获取类型
收费全文 | 1471篇 |
免费 | 60篇 |
国内免费 | 202篇 |
专业分类
化学 | 1642篇 |
晶体学 | 3篇 |
力学 | 1篇 |
综合类 | 11篇 |
数学 | 3篇 |
物理学 | 73篇 |
出版年
2024年 | 1篇 |
2023年 | 18篇 |
2022年 | 117篇 |
2021年 | 95篇 |
2020年 | 58篇 |
2019年 | 54篇 |
2018年 | 30篇 |
2017年 | 38篇 |
2016年 | 61篇 |
2015年 | 72篇 |
2014年 | 49篇 |
2013年 | 76篇 |
2012年 | 199篇 |
2011年 | 81篇 |
2010年 | 58篇 |
2009年 | 87篇 |
2008年 | 97篇 |
2007年 | 96篇 |
2006年 | 76篇 |
2005年 | 75篇 |
2004年 | 57篇 |
2003年 | 39篇 |
2002年 | 32篇 |
2001年 | 19篇 |
2000年 | 19篇 |
1999年 | 15篇 |
1998年 | 19篇 |
1997年 | 16篇 |
1996年 | 20篇 |
1995年 | 11篇 |
1994年 | 11篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 5篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 4篇 |
排序方式: 共有1733条查询结果,搜索用时 15 毫秒
231.
Novel azo linked substituted benzimidazole, benzoxazole, and benzothiazole were synthesized by diazo coupling and characterized by 1H NMR, elemental analysis, FTIR and UV–vis spectroscopy. The newly synthesized compounds were evaluated for invitro antibacterial activity against Staphylococcus aureus and Escherichia Coli strains by Resazurin microtiter assay method (REMA). The minimum inhibitory concentration (MIC in μg/mL) were used to express the antibacterial activities. The azo linked compounds exhibited good to moderate or high antibacterial activities in vitro. Computational studies were performed to correlate HOMO-LUMO gap with antibacterial activity. The comparative molecular docking studies revealed better insights into binding mechanisms. 相似文献
232.
The analysis of vitamin D status, with special emphasis on 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, is gaining interest in clinical studies due to the classical and non-classical effects attributed to this prohormone. In this research, the influence of the two steps preceding determination (viz. sample collection and preparation) on the quantitative analysis of vitamin D and its more important metabolites has been studied. Two preparation approaches, deproteination and solid-phase extraction (SPE), have been evaluated in terms of sensitivity to delimit their application, thus establishing that detection of 1,25-dihydroxyvitamin D cannot be addressed by protein precipitation. Concerning sample collection, serum and plasma reported high accuracy (above 83.3%) for vitamin D and metabolites, while precision, expressed as relative standard deviation, was below 12.9% for all analytes in both samples. Statistical analysis revealed that serum and plasma provided similar physiological levels for vitamin D3, 24,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3, while significantly different levels were obtained for 1,25-dihydroxyvitamin D3, always higher in plasma than in serum. Sample collection and treatment have proved to be significant in the analysis of vitamin D and its relevant metabolites. 相似文献
233.
Maia I. Kelly Tyler J. Bechtel D. Rajasekhar Reddy Erome D. Hankore Jon R. BeckCliff I. Stains 《Analytica chimica acta》2015
Inhibitors of Rho-associated protein kinase (ROCK) enzymatic activity have been shown to reduce the invasive phenotype observed in metastatic hepatocellular carcinoma (HCC). We describe the design, synthesis, and evaluation of a direct probe for ROCK activity utilizing a phosphorylation-sensitive sulfonamido-oxine fluorophore, termed Sox. The Sox fluorophore undergoes an increase in fluorescence upon phosphorylation of a proximal amino acid via chelation-enhanced fluorescence (CHEF, ex. = 360 nm and em. = 485 nm), allowing for the direct visualization of the rate of phosphate addition to a peptide substrate over time. Our optimal probe design, ROCK-S1, is capable of sensitively reporting ROCK activity with a limit of detection of 10 pM and a high degree of reproducibility (Z’-factor = 0.6 at 100 pM ROCK2). As a proof-of-principle for high-throughput screening (HTS) we demonstrate the ability to rapidly assess the efficacy of a 78 member, small molecule library against ROCK2 using a robotics platform. We identify two previously unreported ROCK2 inhibitor scaffolds, PHA665752 and IKK16, with IC50 values of 3.6 μM and 247 nM respectively. Lastly, we define conditions for selectively monitoring ROCK activity in the presence of potential off-target enzymes (PKCα, PKA, and PAK) with similar substrate specificities. 相似文献
234.
235.
A method for the determination of lead is described using thiol-functionalized gold nanoparticle. The detection method is based on the prevention of thiol-induced aggregation of gold nanoparticles by lead. Among six thiols, e.g., 4-mercapto-1-butanol, meso-2, 3-dimercaptosuccinic acid, mercaptosuccinic acid, 6-mercapto-1-hexanol, 4-(methylthio)-1-butanol, 1-propanethiol, four (4-mercapto-1-butanol, 6-mercapto-1-hexanol, 4-(methylthio)-1-butanol and 1-propanethiol) induced the aggregation of the gold nanoparticles which was measured by the change in absorbance at 520 and 650?nm. Prior incubation of the gold nanoparticles with lead decreased the 4-(methylthio)-1-butanol-induced aggregation of gold nanoparticles in a dose-dependent manner. A linear inverse relationship between the logarithmic concentration of lead and the ratio of absorbance at 650 to 520 was noted. The method has a dynamic range from 10?nM to 100?µM. However, metals such as mercury and chromium were more effective in comparison with lead in preventing the 4-methylthio-1-butanol-induced aggregation of gold nanoparticles. The method can be used for assessing the heavy metal load in water samples. 相似文献
236.
An in vitro, rapid, and quantitative cell-based assay is needed to predict the efficacy of cancer drugs in individual patients,
because a cancer patient may have unconventional aspects of tumor development. Here we report a rapid and label-free quantitative
method for verifying apoptosis in living cancer cells cultured on a sensor chip with a newly developed high-precision surface
plasmon resonance (SPR) sensor. The time-course cell reaction was monitored as the SPR angle change rate for 5 min during
a 35-min cell culture of pancreatic cancer lines with a drug. The time-course cell reaction was significantly related to cell
viability counted after 48 h as assessed by caspase-3 activity assay of apoptosis. Furthermore, the detected SPR signal was
derived from the decrease in inner mitochondrial membrane potential. The results obtained are universally valid for various
cancer drugs mediating apoptosis through different cell-signaling pathways and even for combined use in various pancreatic
cancer cell lines. This system can be applied in a clinical setting to evaluate the personal therapeutic potential of drugs
including pharmacodynamic interactions. 相似文献
237.
Wenger D Gerecke AC Heeb NV Naegeli H Zenobi R 《Analytical and bioanalytical chemistry》2008,390(8):2021-2029
An in vitro reporter gene assay based on human breast cancer T47D cells (ER-CALUX) was applied to examine the ability of diesel exhaust to induce or inhibit estrogen receptor (ER)-mediated gene expression. Exhaust from a heavy-duty diesel engine was either treated by iron- or copper/iron-catalyzed diesel particulate filters (DPFs) or studied as unfiltered exhaust. Collected samples included particle-bound and semivolatile constituents of diesel exhaust. Our findings show that all of the samples contained compounds that were able to induce ER-mediated gene expression as well as compounds that suppressed the activity of the endogenous hormone 17beta-estradiol (E2). Estrogenic activity prevailed over antiestrogenic activity. We found an overall ER-mediated activity of 1.63 +/- 0.31 ng E2 CALUX equivalents (E2-CEQs) per m(3) of unfiltered exhaust. In filtered exhaust, we measured 0.74 +/- 0.07 (iron-catalyzed DPF) and 0.55 +/- 0.09 ng E2-CEQ m(-3) (copper/iron-catalyzed DPF), corresponding to reductions in estrogenic activity of 55 and 66%, respectively. Our study demonstrates that both catalytic DPFs lowered the ER-mediated endocrine-disrupting potential of diesel exhaust. 相似文献
238.
We describe the development and validation of a high-resolution screening (HRS) platform which couples gradient reversed-phase
high-performance liquid chromatography (RP-HPLC) on-line to estrogen receptor α (ERα) affinity detection using fluorescence
polarization (FP). FP, which allows detection at high wavelengths, limits the occurrence of interference from the autofluorescence
of test compounds in the bioassay. A fluorescein-labeled estradiol derivative (E2-F) was synthesized and a binding assay was
optimized in platereader format. After subsequent optimization in flow-injection analysis (FIA) mode, the optimized parameters
were translated to the on-line HRS bioassay. Proof of principle was demonstrated by separating a mixture of five compounds
known to be estrogenic (17β-estradiol, 17α-ethinylestradiol and the phytoestrogens coumestrol, coumarol and zearalenone),
followed by post-column bioaffinity screening of the individual affinities for ERα. Using the HRS-based FP setup, we were
able to screen affinities of off-line-generated metabolites of zearalenone for ERα. It is concluded that the on-line FP-based
bioassay can be used to screen for the affinity of compounds without the disturbing occurrence of autofluorescence. 相似文献
239.
Adrian J Pinacho DG Granier B Diserens JM Sánchez-Baeza F Marco MP 《Analytical and bioanalytical chemistry》2008,391(5):1703-1712
A multianalyte ELISA has been developed for the simultaneous determination of the most frequently used antibiotic families in the veterinary field following the typical planar microarray configuration, where the identity of the target analyte is encoded by its location in the detection platform (Master et al. in Drug Discovery Today 11:1007-1011, 2006). To accomplish this aim, two individual enzyme-linked immunosorbent assays for sulfonamide and fluoroquinolone antibiotics and an enzyme-linked receptor assay for ss-lactam antibiotics have been combined. The strategy uses microplates coated with the corresponding haptenized proteins in specific sections of the microplate. The samples are mixed with a cocktail containing the bioreagents, and distributed in the wells of the microplate. Identification of the antibiotic present in a particular sample is consequently accomplished by detecting a positive response on the corresponding microplate section. Since the bioreceptors used show a wide recognition of the congeners of each antibiotic family, the multianalyte method is able to detect more than 25 different antibiotics from the three most important antibiotic families. The detectability reached in full-fat milk samples is below the European maximum residue limits. The accuracy and reliability of this multiplexed bioanalytical method have been demonstrated by analyzing blind spiked samples. 相似文献
240.
Paraskevas D. Tzanavaras Constantinos K. Zacharis 《Central European Journal of Chemistry》2008,6(2):140-144
Three simple protocols for the extraction of acyclovir from its pharmaceutical creams based on ultrasonication, ultrasonication
with heating and magnetic stirring were evaluated and compared. Extraction kinetics were studied at different time intervals
(5, 10, 15, 30 and 60 min) and the extraction efficiency was determined by HPLC. The effect of concentration of aqueous NaOH
as the extraction medium and the stirring speed were also studied and optimized. Best results were obtained with 50 mL of
0.01 mol L−1 aqueous NaOH with magnetic stirring speed of 500 r.p.m. HPLC analysis involved rapid separation of acyclovir from the cream
matrix using a 100 × 4.6 mm i.d. monolithic column and UV detection at 254 nm. Magnetic stirring produced the best results
in terms of extraction efficiency with an average extraction yield of 100.8%, n = 16 at an optimum extraction time of 15 min. The selected protocol was validated for within and day-to-day precision and
ruggedness.
相似文献