全文获取类型
收费全文 | 1452篇 |
免费 | 134篇 |
国内免费 | 194篇 |
出版年
2023年 | 19篇 |
2022年 | 33篇 |
2021年 | 44篇 |
2020年 | 47篇 |
2019年 | 69篇 |
2018年 | 57篇 |
2017年 | 66篇 |
2016年 | 52篇 |
2015年 | 55篇 |
2014年 | 66篇 |
2013年 | 144篇 |
2012年 | 64篇 |
2011年 | 61篇 |
2010年 | 56篇 |
2009年 | 91篇 |
2008年 | 88篇 |
2007年 | 95篇 |
2006年 | 86篇 |
2005年 | 78篇 |
2004年 | 49篇 |
2003年 | 49篇 |
2002年 | 39篇 |
2001年 | 33篇 |
2000年 | 33篇 |
1999年 | 24篇 |
1998年 | 22篇 |
1997年 | 22篇 |
1996年 | 14篇 |
1995年 | 15篇 |
1994年 | 13篇 |
1993年 | 15篇 |
1992年 | 18篇 |
1991年 | 19篇 |
1990年 | 18篇 |
1989年 | 5篇 |
1988年 | 10篇 |
1987年 | 8篇 |
1986年 | 9篇 |
1985年 | 12篇 |
1984年 | 18篇 |
1983年 | 12篇 |
1982年 | 13篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 10篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1974年 | 3篇 |
排序方式: 共有1780条查询结果,搜索用时 15 毫秒
1.
2.
J. Karjalainen A. Kanervo M.-L. Väisänen B. Forsblom E. Sarkiala H. Jousimies-Somer 《FEMS immunology and medical microbiology》1993,6(2-3):207-212
Abstract A total of 259 Gram-negative Porphyromonas -like rods isolated from subgingival plaque samples of 16 family-owned dogs with naturally occurring periodontitis were characterized phenotypically by biochemical reactions, metabolic end products and enzymatic activities (API-ZYMTM , RoscoTM ). Four distinct groups were found. Group A isolates (63) were asaccharolytic, lipase negative, trypsin positive and produced phenylacetic acid (PAA) from peptone-yeast extract glucose broth. Unlike P. gingivalis strains they were catalase positive. Group B isolates (42) differed from those of group A by a positive lipase reaction and from those of group D by failing to ferment sugars. Group C isolates (88) were asaccharolytic and did not produce PAA. They were α-fucosidase, N -acetyl- β -glucosaminidase (β-NAG) and trypsin negative, resembling P. endodontalis , but unlike human isolates, they were catalase positive. Subgroup C.1 isolates (6) differed from those of parent group C by producing minor amounts of PAA, and subgroup C.2 isolates (12) were β-NAG positive. Group D isolates (46) were weakly fermentative, lipase, catalase and trypsin positive, and produced PAA. They resembled the B. (P.) salivosus type strain which, in our hands, fermented weakly glucose, lactose and mannose. Two isolates could not be assigned to any of the previous groups. 相似文献
3.
Herbert Budzikiewicz Mathias Schäfer Diana Uría Fernández Sandra Matthijs Pierre Cornelis 《Biometals》2007,20(2):135-144
Characteristic fragment ions of the various chromophores of the pyoverdin siderophore family obtained by collision activated
dissociation of the [M+2H]2+ ions are reported allowing unambiguous identification. Tandem mass spectrometrical studies revealed the existence of the
first example of a ferribactin with a succinamide side chain, and they add some information to the problem in which way a
malic acid side chain is attached to the chromophore. 相似文献
4.
《Bioorganic & medicinal chemistry》2016,24(18):4444-4451
Nowadays, AT1 receptor (AT1R) antagonists (ARBs) constitute the one of the most prevalent classes of antihypertensive drugs that modulate the renin-angiotensin system (RAS). Their main uses include also treatment of diabetic nephropathy (kidney damage due to diabetes) and congestive heart failure. Towards this direction, our study has been focused on the discovery of novel agents bearing different scaffolds which may evolve as a new class of AT1 receptor antagonists. To fulfill this aim, a combination of computational approaches and biological assays were implemented. Particularly, a pharmacophore model was established and served as a 3D search query to screen the ChEMBL15 database. The reliability and accuracy of virtual screening results were improved by using molecular docking studies. In total, 4 compounds with completely diverse chemical scaffolds from potential ARBs, were picked and tested for their binding affinity to AT1 receptor. Results revealed high nanomolar to micromolar affinity (IC50) for all the compounds. Especially, compound 4 exhibited a binding affinity of 199 nM. Molecular dynamics simulations were utilized in an effort to provide a molecular basis of their binding to AT1R in accordance to their biological activities. 相似文献
5.
《Saudi Journal of Biological Sciences》2022,29(6):103287
Triphala is a famous triherbal drug, comprising three herb fruits, including Terminalia chebula (Haritaki), Terminalia bellirica (Bibhitaki), and Phyllanthus emblica (Amalaki). It is enriched with vitamin C, polyphenols, flavonoids, sterols, saponins, etc., and is well-documented for its potent antioxidant, anticancer, chemoprotective, antimicrobial, and anti-inflammatory effects. This research was conducted to evaluate the synergistic antioxidative and cytotoxic potential of mixtures of the individual constituents of Triphala at their nonequivalent ratios along with the chemical characterization of individual constituents of Triphala to identify and quantify individual compounds. The antioxidative potential was measured using total antioxidant capacity (TAC), DPPH free radical scavenging assay, and total phenolic content (TPC) tests. The cytotoxic potential was assessed on brain cancer cells (N4X4) using MTT assay, and phytochemical characterization was performed by GS-MS analysis. Nonequivalent ratios of Triphala constituents exhibited significantly higher synergistic antioxidant and cytotoxic potential than the equivalent ratios of them. Moreover, the nonequivalent ratio where the quantity of Amalaki was doubled than the other two constituents showed the highest synergistic antioxidant and cytotoxic effect. GC-MS analysis of individual constituents of Triphala identified and quantified the presence of a wide array of compounds, and fatty acid, fatty acid ester, triterpene, and aminoglycoside remained the predominant class of compounds. Thus, it can be inferred that the observed bioactivities can be attributed to the phytocompounds characterized and extracts at the nonequivalent ratio of Triphala constituents where Amalaki is doubled can be more effective in treating oxidative degenerative diseases and glioblastoma. 相似文献
6.
H. Chen L. Wang C.X. Su G.H. Gong P. Wang Z.L. Yu 《Letters in applied microbiology》2008,47(3):180-186
Aims: Antibiotics from Bacillus subtilis JA show strong pathogen inhibition ability, which has potential market application; yet, the composition of these antibiotics has not been elucidated. The aim of this paper is to isolate and identify these antibiotics.
Methods and Results: The antagonistic activity of JA was tested in vitro ; it exhibited strong inhibition against some important phytopathogens and postharvest pathogens. Crude antibiotic production was extracted with methanol from the precipitate by adding 6 mol l−1 HCl to the bacillus-free culture broth. The crude extract was run on Diamonsil C18 column (5 μ m, 250 × 4·6 mm) in HPLC system to separate the antibiotics. Major antibiotics were classified into three lipopeptide families according to electrospray ionization–mass spectrometry analysis. Subsequently, the classification of antibiotics was confirmed with typical collision-induced dissociation fragments.
Conclusions: Three kinds of antibiotics were isolated from B. subtilis JA and were identified to the lipopeptide families, surfactin, iturin and fengycin. These compounds could function as biocontrol agents against a large spectrum of pathogens.
Significance and Impact of the Study: This study provided a reliable and rapid method for isolation and structural characterization of lipopeptide antibiotics from B. subtilis . 相似文献
Methods and Results: The antagonistic activity of JA was tested in vitro ; it exhibited strong inhibition against some important phytopathogens and postharvest pathogens. Crude antibiotic production was extracted with methanol from the precipitate by adding 6 mol l
Conclusions: Three kinds of antibiotics were isolated from B. subtilis JA and were identified to the lipopeptide families, surfactin, iturin and fengycin. These compounds could function as biocontrol agents against a large spectrum of pathogens.
Significance and Impact of the Study: This study provided a reliable and rapid method for isolation and structural characterization of lipopeptide antibiotics from B. subtilis . 相似文献
7.
The present study optimized the extraction characterization and antioxidant activities of water-soluble compound polysaccharides (CPs) from hawthorn, lotus leaf, Fagopyrum tataricum, semen cassiae, Lycium barbarum, and Poria cocos Chinese herbal medicines that have mass ratios of 4 : 2 : 2 : 1.5 : 1 : 1. The CPs yield equation was predicted using quantitative theory, to which a maximum CPs yield of 7.18±0.24 % under the following optimal extraction conditions: a water-to-raw material ratio of 30 mL/g, an extraction temperature of 65 °C, an extraction time of 45 min, and extraction mode ultrasonic-assistant extraction. CPs were consisted of Ara, Gal, Glc, Xyl, Man, GalA and GlcA in a molar ratio of 3.1 : 2.6 : 50.6 : 1.7 : 20.4 : 17.2 : 4.2. The HPGPC profiles and FT-IR spectra implied that CPs were heterogeneous acidic polysaccharides and possessed the β-d -pyranose configuration. Congo red test, CD spectrum and SEM revealed that CPs with three helix conformation showed a flocculent, granulous or sheet-like appearance. Furthermore, the relationships between antioxidant activity and concentration of CPs displayed significant positive correlation, and the scavenging abilities for DPPH, hydroxyl radical, ABTS, superoxide-anion radical and reducing power of CPs were 93.56±2.51 %, 84.03±1.69 %, 83.29±1.93 %, 37.49±1.93 % and 0.467±0.006 at a concentration of 4.0 mg/mL. Therefore, CPs could be applied as a potential natural antioxidant in pharmaceutical or functional food fields. 相似文献
8.
The kinetic properties of rat liver nuclear lysozyme, earlier purified to homogeneity in our laboratory, have been studied.
The enzyme was found to be maximally active in the pH range 4.2 to 5.4 in 0.02 M buffer. Its Km was found to be 333 mg/litre.
It was heat sensitive even in the acidic pH range. The enzyme exhibited tissue specific differences when compared with the
rat kidney nuclear lysozyme. 相似文献
9.
The membrane-bound atrial natriuretic peptide receptor (GCA) catalyzes the formation of cGMP from GTP in response to natriuretic peptide hormones. Previous structural studies have focused on the extra-cellular hormone binding domain of this receptor whereas its intra-cellular domain has not yet been amenable to such studies. We report here the baculovirus expression and purification of the GCA intra-cellular domain construct GCAID comprising the complete intra-cellular region which includes the kinase-homology domain, coiled-coil region, and catalytic cyclase domain. The intra-cellular domain was enzymatically characterized in terms of guanylyl cyclase activity and the effects of ATP, manganese, and Triton X-100. Our results indicate that the activity of the intra-cellular domain of the ANP receptor is about 2 fold less active compared to a truncated cyclase domain construct lacking the kinase-like domain that was also expressed and purified. In addition, unlike the full length receptor, the intra-cellular domain could not be activated by Triton X-100/Mn2+ or its activity stimulated by ATP. These data therefore indicate that the major part of the transition from the basal state to the fully, ANP/ATP-dependent, activated state as well its stimulation/enhancement by Triton X-100/Mn2+ requires the full length receptor. These receptor insights could aid in the development of novel therapeutics as the GCA receptor is a key drug target for cardiovascular diseases. 相似文献
10.
T. Noelle Lombana Jack Bevers III Amy M. Berkley Evangeline Toy Ryan Cook 《MABS-AUSTIN》2019,11(1):75-93
As an immune evasion strategy, MICA and MICB, the major histocompatibility complex class I homologs, are proteolytically cleaved from the surface of cancer cells leading to impairment of CD8 + T cell- and natural killer cell-mediated immune responses. Antibodies that inhibit MICA/B shedding from tumors have therapeutic potential, but the optimal epitopes are unknown. Therefore, we developed a high-resolution, high-throughput glycosylation-engineered epitope mapping (GEM) method, which utilizes site-specific insertion of N-linked glycans onto the antigen surface to mask local regions. We apply GEM to the discovery of epitopes important for shedding inhibition of MICA/B and validate the epitopes at the residue level by alanine scanning and X-ray crystallography (Protein Data Bank accession numbers 6DDM (1D5 Fab-MICA*008), 6DDR (13A9 Fab-MICA*008), 6DDV (6E1 Fab-MICA*008). Furthermore, we show that potent inhibition of MICA shedding can be achieved by antibodies that bind GEM epitopes adjacent to previously reported cleavage sites, and that these anti-MICA/B antibodies can prevent tumor growth in vivo. 相似文献