全文获取类型
收费全文 | 1931篇 |
免费 | 85篇 |
国内免费 | 43篇 |
出版年
2023年 | 25篇 |
2022年 | 20篇 |
2021年 | 35篇 |
2020年 | 29篇 |
2019年 | 38篇 |
2018年 | 44篇 |
2017年 | 31篇 |
2016年 | 35篇 |
2015年 | 56篇 |
2014年 | 68篇 |
2013年 | 108篇 |
2012年 | 59篇 |
2011年 | 78篇 |
2010年 | 57篇 |
2009年 | 52篇 |
2008年 | 56篇 |
2007年 | 66篇 |
2006年 | 62篇 |
2005年 | 57篇 |
2004年 | 51篇 |
2003年 | 60篇 |
2002年 | 62篇 |
2001年 | 39篇 |
2000年 | 49篇 |
1999年 | 42篇 |
1998年 | 35篇 |
1997年 | 25篇 |
1996年 | 27篇 |
1995年 | 34篇 |
1994年 | 21篇 |
1993年 | 16篇 |
1992年 | 24篇 |
1991年 | 27篇 |
1990年 | 23篇 |
1989年 | 22篇 |
1988年 | 25篇 |
1987年 | 35篇 |
1986年 | 15篇 |
1985年 | 34篇 |
1984年 | 44篇 |
1983年 | 47篇 |
1982年 | 57篇 |
1981年 | 43篇 |
1980年 | 62篇 |
1979年 | 44篇 |
1978年 | 29篇 |
1977年 | 25篇 |
1976年 | 20篇 |
1975年 | 11篇 |
1974年 | 18篇 |
排序方式: 共有2059条查询结果,搜索用时 78 毫秒
121.
《Bioscience, biotechnology, and biochemistry》2013,77(12):3277-3280
Cyclic isomaltooligosaccharides (CIs) usually consist of 7 to 12 glucose units, although only CI-10 has strong inclusion complex-forming ability. Four Bacillus strains and two Paenibacillus strains were isolated as novel CI-producing bacteria. Among these, five strains produced small amounts of CI-7 to CI-9, but mainly produced CI-10 to CI-12. Larger CIs, up to CI-17, were also identified. 相似文献
122.
On‐chip assessment of human primary cardiac fibroblasts proliferative responses to uniaxial cyclic mechanical strain 下载免费PDF全文
123.
High levels of cyclic‐di‐GMP in plant‐associated Pseudomonas correlate with evasion of plant immunity 下载免费PDF全文
Sebastian Pfeilmeier Isabel Marie‐Luise Saur John Paul Rathjen Cyril Zipfel Jacob George Malone 《Molecular Plant Pathology》2016,17(4):521-531
The plant innate immune system employs plasma membrane‐localized receptors that specifically perceive pathogen/microbe‐associated molecular patterns (PAMPs/MAMPs). This induces a defence response called pattern‐triggered immunity (PTI) to fend off pathogen attack. Commensal bacteria are also exposed to potential immune recognition and must employ strategies to evade and/or suppress PTI to successfully colonize the plant. During plant infection, the flagellum has an ambiguous role, acting as both a virulence factor and also as a potent immunogen as a result of the recognition of its main building block, flagellin, by the plant pattern recognition receptors (PRRs), including FLAGELLIN SENSING2 (FLS2). Therefore, strict control of flagella synthesis is especially important for plant‐associated bacteria. Here, we show that cyclic‐di‐GMP [bis‐(3′‐5′)‐cyclic di‐guanosine monophosphate], a central regulator of bacterial lifestyle, is involved in the evasion of PTI. Elevated cyclic‐di‐GMP levels in the pathogen Pseudomonas syringae pv. tomato (Pto) DC3000, the opportunist P. aeruginosa PAO1 and the commensal P. protegens Pf‐5 inhibit flagellin synthesis and help the bacteria to evade FLS2‐mediated signalling in Nicotiana benthamiana and Arabidopsis thaliana. Despite this, high cellular cyclic‐di‐GMP concentrations were shown to drastically reduce the virulence of Pto DC3000 during plant infection. We propose that this is a result of reduced flagellar motility and/or additional pleiotropic effects of cyclic‐di‐GMP signalling on bacterial behaviour. 相似文献
124.
Andrea Pinto Lucia Tamborini Eugenia Pennacchietti Antonio Coluccia Romano Silvestri Gregorio Cullia 《Journal of enzyme inhibition and medicinal chemistry》2016,31(2):295-301
The γ-aminobutyrate (GABA)-degradative enzyme GABA aminotransferase (GABA-AT) is regarded as an attractive target to control GABA levels in the central nervous system: this has important implications in the treatment of several neurological disorders and drug dependencies. We have investigated the ability of newly synthesized compounds to act as GABA-AT inhibitors. These compounds have a unique bicyclic structure: the carbocyclic ring bears the GABA skeleton, while the fused 3-Br-isoxazoline ring contains an electrophilic warhead susceptible of nucleophilic attack by an active site residue of the target enzyme. Out of the four compounds tested, only the one named (+)-3 was found to significantly inhibit mammalian GABA-AT in vitro. Docking studies, performed on the available structures of GABA-AT, support the experimental findings: out of the four tested compounds, only (+)-3 suitably orients the electrophilic 3-Br-isoxazoline warhead towards the active site nucleophilic residue Lys329, thereby explaining the irreversible inhibition of GABA-AT observed experimentally. 相似文献
125.
Spectroscopic,electrochemical and molecular docking studies of dothiepin and doxepin with bovine serum albumin and DNA base 下载免费PDF全文
The interaction of dothiepin (DOT) and doxepin (DOX) with bovine serum albumin (BSA) and a DNA base (adenine) was studied using UV–visible, fluorescence, attenuated total reflection–infra‐red (ATR‐IR), cyclic voltammetry and molecular docking methods. Strong fluorescence quenching was observed upon interaction of DOT and DOX with BSA/adenine and the mechanism suggested static quenching. Hydrophobic and hydrogen bonding interactions were the predominant intermolecular forces needed to stabilize the copolymer. Upon addition of the drugs: (i) the tautomeric equilibrium structure of the adenine was changed; and (ii) the oxidation and the reduction peaks of the adenine/BSA interaction shifted towards high and low potentials, respectively. In ATR‐IR, the band shift of amides I and II indicated a change in secondary structure of BSA upon binding to DOT and DOX drugs. The reduction in voltammetric current in the presence of BSA/adenine was attributed to slow diffusion of BSA/adenine binding with DOX/DOT. The docking method indicated that the drug moiety interacted with the BSA molecule. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
126.
Correlation between endogenous polyamines in human cardiac tissues and clinical parameters in patients with heart failure 下载免费PDF全文
Carmen Bordallo Lorena Suárez Javier Bordallo Manuel Sánchez 《Journal of cellular and molecular medicine》2016,20(2):302-312
Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase in ornithine decarboxylase (ODC) activity and intracellular polyamines associated with cyclic adenosine monophosphate (cAMP) increases. The aim of the study was to establish the role of these in the human heart in living patients. For this, polyamines (by high performance liquid chromatography) and the activity of ODC and N1‐acetylpolyamine oxidases (APAO) were determined in the right atrial appendage of 17 patients undergoing extracorporeal circulation to correlate with clinical parameters. There existed enzymatic activity associated with the homeostasis of polyamines. Left atria size was positively associated with ODC (r = 0.661, P = 0.027) and negatively with APAO‐N1‐acetylspermine (r = −0.769, P = 0.026), suggesting that increased levels of polyamines are associated with left atrial hemodynamic overload. Left ventricular ejection fraction (LVEF) and heart rate were positively associated with spermidine (r = 0.690, P = 0.003; r = 0.590, P = 0.021) and negatively with N1‐acetylspermidine (r = −0.554, P = 0.032; r = −0.644, P = 0.018). LVEF was negatively correlated with cAMP levels (r = −0.835, P = 0.001) and with cAMP/ODC (r = −0.794, P = 0.011), cAMP/spermidine (r = −0.813, P = 0.001) and cAMP/spermine (r = −0.747, P = 0.003) ratios. Abnormal LVEF patients showed decreased ODC activity and spermidine, and increased N1‐acetylspermidine, and cAMP. Spermine decreased in congestive heart failure patients. The trace amine isoamylamine negatively correlated with septal wall thickness (r = −0.634, P = 0.008) and was increased in cardiac heart failure. The results indicated that modifications in polyamine homeostasis might be associated with cardiac function and remodelling. Increased cAMP might have a deleterious effect on function. Further studies should confirm these findings and the involvement of polyamines in different stages of heart failure. 相似文献
127.
Patrycja Rogala Grzegorz Czerwonka Sawomir Michakiewicz Maciej Hodorowicz Barbara Barszcz Agnieszka Jaboska‐Wawrzycka 《化学与生物多样性》2019,16(11)
The antibacterial and antibiofilm activities of two new ruthenium complexes against E. coli, S. aureus, P. aeruginosa PAO1 (laboratory strain) and P. aeruginosa LES B58 (clinical strain) were evaluated. Complexes, mer‐[RuIII(2‐bimc)3] ? H2O ( 1 ) and cis‐[RuIVCl2(2,3‐pydcH)2] ? 4H2O ( 2 ), were obtained using aromatic carboxylic acid ligands, namely, 1H‐benzimidazole‐2‐carboxylic acid (2‐bimcH) and pyridine‐2,3‐dicarboxylic acid (2,3‐pydcH2). Compounds were physicochemically characterized using X‐ray diffraction, Hirshfeld surface analysis, IR and UV/VIS spectroscopies, as well as magnetic and electrochemical measurements. Structural characterization revealed that Ru(III) and Ru(IV) ions in the complexes adopt a distorted octahedral geometry. The intermolecular classical and weak hydrogen bonds, and π???π contacts significantly contribute to structure stabilization, leading to the formation of a supramolecular assembly. Biological studies have shown that the Ru complexes inhibit the growth of bacteria and biofilm formation by the tested strains and the complexes seem to be a potential as antimicrobial agents. 相似文献
128.
《Harmful algae》2019
Cyanobacterial blooms occur when algal densities exceed baseline population concentrations. Cyanobacteria can produce a large number of secondary metabolites. Odorous metabolites affect the smell and flavor of aquatic animals, whereas bioactive metabolites cause a range of lethal and sub-lethal effects in plants, invertebrates, and vertebrates, including humans. Herein, the bioactivity, chemistry, origin, and biosynthesis of these cyanobacterial secondary metabolites were reviewed. With recent revision of cyanobacterial taxonomy by Anagnostidis and Komárek as part of the Süβwasserflora von Mitteleuropa volumes 19(1–3), names of many cyanobacteria that produce bioactive compounds have changed, thereby confusing readers. The original and new nomenclature are included in this review to clarify the origins of cyanobacterial bioactive compounds.Due to structural similarity, the 157 known bioactive classes produced by cyanobacteria have been condensed to 55 classes. This review will provide a basis for more formal procedures to adopt a logical naming system. This review is needed for efficient management of water resources to understand, identify, and manage cyanobacterial harmful algal bloom impacts. 相似文献
129.
130.
The selective delivery of therapeutic agents to receptors overexpressed in cancer cells without harming the rest of the body is a major challenge in clinical oncology today. In this study, we report the design and synthesis of paclitaxel (PTX) conjugated with an erbB2-recognizing peptide (EC-1). The cyclic peptide EC-1 specifically binds to the extracellular domain of ErbB2 and selectively inhibits proliferation of breast cancer cells overexpressing ErbB2. PTX is a potent antitumor agent commonly used in the treatment of advanced metastatic breast cancer, yet patients have to suffer some side effects caused by its systemic toxicity. The aim of our conjugate is to specifically deliver antitumor agent PTX to breast cancer cells that overexpress oncogenic ErbB2 with the purpose to reduce toxicity and enhance selective killing of cancer cells. In this study, a concise and efficient synthetic route for the preparation of the PTX-EC-1 conjugate has been developed in 6% overall yield. This synthetic approach provides a general method for conjugating a highly functionalized and disulfide-bridge containing cyclopeptide to Taxol or other antitumor agents. 相似文献