全文获取类型
收费全文 | 836篇 |
免费 | 59篇 |
国内免费 | 1篇 |
专业分类
896篇 |
出版年
2024年 | 1篇 |
2023年 | 16篇 |
2022年 | 28篇 |
2021年 | 39篇 |
2020年 | 27篇 |
2019年 | 35篇 |
2018年 | 48篇 |
2017年 | 24篇 |
2016年 | 45篇 |
2015年 | 55篇 |
2014年 | 70篇 |
2013年 | 64篇 |
2012年 | 85篇 |
2011年 | 79篇 |
2010年 | 48篇 |
2009年 | 27篇 |
2008年 | 47篇 |
2007年 | 27篇 |
2006年 | 33篇 |
2005年 | 27篇 |
2004年 | 23篇 |
2003年 | 18篇 |
2002年 | 6篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 1篇 |
排序方式: 共有896条查询结果,搜索用时 10 毫秒
81.
The influence of alkaline and the neutral grade of magnesium aluminometasilicate as a porous solid carrier for the liquid self-emulsifying formulation with ibuprofen is investigated. Ibuprofen is dissolved in Labrasol, then this solution is adsorbed on the silicates. The drug to the silicate ratio is 1:2, 1:4, and 1:6, respectively. The properties of formulations obtained are analyzed, using morphological, porosity, crystallinity, and dissolution studies. Three solid self-emulsifying (S-SE) formulations containing Neusilin SG2 and six consisting of Neusilin US2 are in the form of powder without agglomerates. The nitrogen adsorption method shows that the solid carriers are mesoporous but they differ in a specific surface area, pore area, and the volume of pores. The adsorption of liquid SE formulation on solid silicate particles results in a decrease in their porosity. If the neutral grade of magnesium aluminometasilicate is used, the smallest pores, below 10 nm, are completely filled with liquid formulation, but there is still a certain number of pores of 40–100 nm. Dissolution studies of liquid SEDDS carried out in pH = 1.2 show that Labrasol improves the dissolution of ibuprofen as compared to the pure drug. Ibuprofen dissolution from liquid SE formulations examined in pH of 7.2 is immediate. The adsorption of the liquid onto the particles of the silicate causes a decrease in the amount of the drug released. Finally, more ibuprofen is dissolved from S-SE that consist of the neutral grade of magnesium aluminometasilicate than from the formulations containing the alkaline silicate.KEY WORDS: dissolution, ibuprofen, labrasol, magnesium aluminometasilicate, self-emulsifying powder 相似文献
82.
Cobalt(II) complexes with 6-(2-hydroxybenzylamino)purine (HL1), 6-(2-methoxybenzylamino)purine (HL2), 6-(3-methoxybenzylamino)purine (HL3) and 6-(4-methoxybenzylamino)purine (HL4) of the composition [Co(L1)Cl(H2O)2].H2O (1), [Co(L2)Cl(H2O)2] (2), [Co(L3)2(H2O)2].2H2O (3), [Co(L4)2(H2O)2].2H2O (4) have been synthesized. The compounds have been characterized by elemental analysis, FT-IR, ES+ MS (electrospray mass spectra in the positive ion mode) and electronic spectroscopies, magnetic and conductivity data as tetrahedral high-spin cobalt(II) complexes. The thermal stability of the complexes has also been studied. The cytotoxicity of the complexes (1-4) was determined by a Calcein acetoxymethyl (AM) assay. Human malignant melanoma (G361), human chronic myelogenous erythroleukemia (K562), human osteogenic sarcoma (HOS) and human breast adenocarcinoma (MCF7) cell lines were used for the testing. The molecular structure of 6-(3-methoxybenzylamino)purinium chloride monohydrate, H2L3+.Cl.H2O, i.e. a protonated form of the free HL(3) ligand, has been determined by a single crystal X-ray analysis. The geometry optimisation and infrared frequencies calculations of HL1, HL2, and H2L3+ and H2L4+ were performed using density-functional theory (DFT) calculations at the B3LYP/6-31G* level of the theory. The geometry of complex (1) was optimised at the same level of the theory. 相似文献
83.
The effect of European beech (Fagus sylvatica) and Norway spruce (Picea abies) on acid deposition and soil water chemistry was studied at a site in the Ore Mts., Czech Republic, that has been subjected to decades of elevated acidic deposition. Dry deposition onto the spruce canopy significantly increased acid input to the soil in comparison to the beech canopy. As a result soil waters were more acidic; Al, SO4(2-), and NO3- concentrations were significantly higher; and Ca and K concentrations were lower in the spruce stand than in the beech stand. The concentrations of potentially toxic inorganic aluminium (Al(in)) were, on average, three times higher in the spruce stand than in the beech stand. Thus, Al played a major role in neutralizing acid inputs to mineral soils in the spruce stand. Despite the higher dissolved organic carbon (DOC) concentrations in spruce organic soil solutions, organic Al (Al(org)) accounted for only 30% of total Al (Al(tot)), whereas in beech organic soil solutions Al(org) was 60% of Al(tot). Soil waters in the beech stand exhibited Al(in) concentrations close to solubility with jurbanite (Al(SO4)OH.5H2O). The more acidic soil waters in the spruce stand were oversaturated with respect to jurbanite. The Bc/Al(in) ratio (Bc = Ca + Mg + K) in O horizon leachate was 4.6 and 70 in spruce and beech stands, respectively. In beech mineral soil solutions, the Bc/Al(in) ratio declined significantly to about 2. In the spruce stand, mineral soil solutions had Bc/Al(in) values below the critical value of 1. The observed Bc/Al(in) value of 0.4 at 30 cm depth in the spruce stand suggests significant stress for spruce rooting systems. A more favourable value of 31 was observed for the same depth in the beech stand. The efficiency of the spruce canopy in capturing acidic aerosols, particulates, and cloud water has resulted in the long-term degradation of underlying soils as a medium for sustainable forest growth. 相似文献
84.
Kruszynski R Fichna J do-Rego JC Janecki T Kosson P Pakulska W Costentin J Janecka A 《Bioorganic & medicinal chemistry》2005,13(24):6713-6717
In this paper, we describe the synthesis of a series of endomorphin-2 analogs containing N-methylated amino acids, consecutively in each position. The μ-opioid receptor binding affinities of the new analogs were determined in the displacement experiments. Their in vivo antinociceptive activity was assessed in the hot-plate test in mice after central (icv) and peripheral (ip) administration. [Sar2]endomorphin-2, which had the highest μ-receptor affinity, also showed the strongest analgesic effect when administered centrally and was the only analog that retained activity after peripheral injection. 相似文献
85.
Surface plasmon resonance (SPR) biosensors are affinity sensing devices exploiting a special mode of electromagnetic field-surface plasmon-polariton-to detect the binding of analyte molecules from a liquid sample to biomolecular recognition elements immobilized on the surface of the sensor. In this paper, we review advances of SPR biosensor technology towards detection systems for the simultaneous detection of multiple analytes (multi-analyte detection). In addition, we report application of a recently developed multichannel SPR sensor based on spectroscopy of surface plasmons and wavelength division multiplexing of sensing channels to multi-analyte detection. 相似文献
86.
Hrebícek M Mrázová L Seyrantepe V Durand S Roslin NM Nosková L Hartmannová H Ivánek R Cízkova A Poupetová H Sikora J Urinovská J Stranecký V Zeman J Lepage P Roquis D Verner A Ausseil J Beesley CE Maire I Poorthuis BJ van de Kamp J van Diggelen OP Wevers RA Hudson TJ Fujiwara TM Majewski J Morgan K Kmoch S Pshezhetsky AV 《American journal of human genetics》2006,79(5):807-819
Mucopolysaccharidosis IIIC (MPS IIIC, or Sanfilippo C syndrome) is a lysosomal storage disorder caused by the inherited deficiency of the lysosomal membrane enzyme acetyl-coenzyme A: alpha -glucosaminide N-acetyltransferase (N-acetyltransferase), which leads to impaired degradation of heparan sulfate. We report the narrowing of the candidate region to a 2.6-cM interval between D8S1051 and D8S1831 and the identification of the transmembrane protein 76 gene (TMEM76), which encodes a 73-kDa protein with predicted multiple transmembrane domains and glycosylation sites, as the gene that causes MPS IIIC when it is mutated. Four nonsense mutations, 3 frameshift mutations due to deletions or a duplication, 6 splice-site mutations, and 14 missense mutations were identified among 30 probands with MPS IIIC. Functional expression of human TMEM76 and the mouse ortholog demonstrates that it is the gene that encodes the lysosomal N-acetyltransferase and suggests that this enzyme belongs to a new structural class of proteins that transport the activated acetyl residues across the cell membrane. 相似文献
87.
Barbara Czakó János Marton Sándor Berényi Katarzyna Gach Jakub Fichna Martin Storr Géza Tóth Attila Sipos Anna Janecka 《Bioorganic & medicinal chemistry》2010,18(10):3535-3542
A set of novel 6-substituted orvinols was synthesized and pharmacologically characterized in order to explore the effect of the polarity and steric effects of these new moieties on the opioid activity. It was revealed that longer 6-O-alkyl chains led to increased agonistic activities, while the lack of C6-etheral oxygen gave rise to an antagonistic profile at the opioid receptors in the mouse ileum. 相似文献
88.
Time-resolved fluorescence of 3-methylbenzimidazole (m3B) was used to study stacking interaction between base moieties in di-, tri- and tetra-phosphate analogues of 3-methylbenzimidazolyl(5′-5′)guanosine (m3Bp
n
G, n = 2, 3, 4), using 5′-triphosphate of 3-methylbenzimidazole riboside (m3BTP) as reference. Fluorescence intensity decays of all compounds cannot be satisfactory fitted with single-exponential function. Although an increase of a number of exponents led to better fits, interpretation of the individual exponential terms, i.e. pre-exponential amplitudes and fluorescence lifetimes, cannot be adequately characterized. We show that these fluorescence decays are best fitted by power-like function derived from physically justified distribution of the fluorescence lifetimes, and characterized by the mean value of the excited-state lifetime and relative variance of lifetime fluctuations around the mean value. The latter led to the parameter of heterogeneity and number of decay paths, which depend on the factors responsible for non-radiative decay of the excited state, including base–base stacking interaction. This was studied by means of changes of temperature and the number of phosphate groups in dinucleotides. It was shown that the strongest effect of stacking interactions, characterized by lowest values of both fluorescence mean decay time and relative variance, occurs in the case of m3Bp3G containing the same number of phosphates as natural mRNA cap. The possible importance of these results for interpretation of the mechanism of function of the mRNA cap structure is discussed. 相似文献
89.
Jacqueline A. Aitkenhead-Peterson Jess E. Alexander Jana Albrechtová Pavel Krám Barrett Rock Pavel Cudlín Jakub Hruška Zuzana Lhotaková Ryan Huntley Filip Oulehle Tomáš Polák William H. McDowell 《Plant and Soil》2006,283(1-2):187-201
Dissolved organic carbon and nitrogen (DOC and DON) produced in the forest floor are important for ecosystem functions such
as microbial metabolism, pedogenesis and pollutant transport. Past work has shown that both DOC and DON production are related
to litterfall and standing stocks of C and N in the forest floor. This study, conducted in spring, 2003, investigated variation
in forest floor water extractable DOC (WEDOC) and DON (WEDON) and forest floor C and N as a function of lignin, cellulose
and N contained in live canopy foliage across eight Picea abies [L.] Karst stands in northern Bohemia. Based on Near Infrared Spectroscopy (NIR) analysis of foliar materials, lignin:N and
cellulose:N content of the youngest needles (those produced in 2002) were positively and significantly related to WEDOC (R2 = 0.82–0.97; P<0.01) and to forest floor C:N ratio (R = 0.72–0.78; P<0.01). Foliar N was strongly and negatively related to WEDOC and C:N ratio (R = −0.91 and 0.72; P<0.05) among our study sites. WEDON was positively correlated to foliar lignin:N (R = 0.48; P<0.05; n=40). Forest floor C pools were not positively correlated with foliar lignin and cellulose and forest floor N pools were not
positively correlated with foliar N. Instead, a significant negative correlation was found between forest floor N pools and
foliar cellulose (R=−0.41; P<0.05), and between forest floor C pools and foliar N (R = −0.44; P<0.05). From a remote sensing standpoint, our results are important because canopy reflectance properties are primarily influenced
by the most recent foliage, and it was the chemistry of the most recently produced needles that showed a stronger relationship
with forest floor WEDOC and C:N ratio suggesting forest floor production of WEDOC can be calculated regionally with remote
sensing. 相似文献
90.
Kwintkiewicz J Spaczynski RZ Foyouzi N Pehlivan T Duleba AJ 《Biology of reproduction》2006,74(6):1034-1040
Insulin and moderate oxidative stress stimulate proliferation of ovarian theca-interstitial cells. The effects of these agents on selected signal transduction pathways were examined. PD98059 (inhibitor of MAP2K1, also known as MEK-1, upstream of extracellular signal-regulated protein kinases MAPK3/1, also known as ERK1/2), wortmannin (inhibitor of PIK3C2A, also known as PI3K), and rapamycin (inhibitor of FRAP1, also known as mTOR, upstream of RPS6KB1) each significantly decreased insulin and oxidative stress-induced proliferation of theca-interstitial cells. The greatest inhibition was observed in the presence of rapamycin; this effect occurred without a significant change in cell viability. Phosphorylation of AKT was stimulated by insulin only, while phosphorylation of MAPK3/1 and RPS6KB1 was increased by insulin and oxidative stress. Insulin-induced and oxidative stress-induced phosphorylation of RPS6KB1 was partly inhibited by wortmannin and partly by PD98059; the greatest inhibition was observed in the presence of a combination of wortmannin plus PD98059. Effects of insulin and oxidative stress on phosphorylation of RPS6KB1 were confirmed by kinase activity assays. These findings indicate that actions of insulin and oxidative stress converge on MAPK3/1 and RPS6KB1. Furthermore, we speculate that activation of RPS6KB1 may be in part induced via the MAPK3/1 pathway. 相似文献