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991.
Janiszewska J Urbanczyk-Lipkowska Z 《Journal of molecular microbiology and biotechnology》2007,13(4):220-225
A concept of application of dendrimer chemistry for construction of 'non-sequential pharmacophore', mimicking active conformation of linear antimicrobial peptides, is introduced. It resulted in the synthesis of a family of low- molecular-weight basic peptide dendrimers with antimicrobial properties against Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative) and Candida albicans. 相似文献
992.
Agne Babusyte Kristina Stravinskaite Jolanta Jeroch Jan Lötvall Raimundas Sakalauskas Brigita Sitkauskiene 《Respiratory research》2007,8(1):81-9
Background
Smoking activates and recruits inflammatory cells and proteases to the airways. Matrix metalloproteinase (MMP)-12 may be a key mediator in smoke induced emphysema. However, the influence of smoking and its cessation on airway inflammation and MMP-12 expression during COPD is still unknown. We aimed to analyse airway inflammatory cell patterns in induced sputum (IS) and bronchoalveolar lavage (BAL) from COPD patients who are active smokers and who have ceased smoking >2 years ago.Methods
39 COPD outpatients – smokers (n = 22) and ex-smokers (n = 17) were studied. 8 'healthy' smokers and 11 healthy never-smokers were tested as the control groups. IS and BAL samples were obtained for differential and MMP-12+-macrophages count analysis.Results
The number of IS neutrophils was higher in both COPD groups compared to both controls. The amount of BAL neutrophils was higher in COPD smokers compared to healthy never-smokers. The number of BAL MMP-12+-macrophages was higher in COPD smokers (1.6 ± 0.3 × 106/ml) compared to COPD ex-smokers, 'healthy' smokers and healthy never-smokers (0.9 ± 0.4, 0.4 ± 0.2, 0.2 ± 0.1 × 106/ml respectively, p < 0.05).Conclusion
The lower amount of BAL neutrophils in COPD ex-smokers, compared to COPD smokers, suggests positive alterations in alveolar compartment after smoking cessation. Smoking and disease itself may stimulate MMP-12 expression in airway compartments (IS and BAL) from COPD patients. 相似文献993.
Vassiliou S Xeilari M Yiotakis A Grembecka J Pawełczak M Kafarski P Mucha A 《Bioorganic & medicinal chemistry》2007,15(9):3187-3200
A novel, general, and versatile method of diversification of the P1' position in phosphinic pseudodipeptides, presumable inhibitors of proteolytic enzymes, was elaborated. The procedure was based on parallel derivatization of the amino group in the suitably protected phosphinate building blocks with appropriate alkyl and aryl halides. This synthetic strategy represents an original approach to phosphinic dipeptide chemistry. Its usefulness was confirmed by obtaining a series of P1' modified phosphinic dipeptides, inhibitors of cytosolic leucine aminopeptidase, through computer-aided design basing on the structure of homophenylalanyl-phenylalanine analogue (hPheP[CH(2)]Phe) bound in the enzyme active site as a lead structure. In this approach novel interactions between inhibitor P1' fragment and the S1' region of the enzyme, particularly hydrogen bonding involving Asn330 and Asp332 enzyme residues, were predicted. The details of the design, synthesis, and activity evaluation toward cytosolic leucine aminopeptidase and aminopeptidase N are discussed. Although the potency of the lead compound has not been improved, marked selectivity of the synthesized inhibitors toward both studied enzymes was observed. 相似文献
994.
Unconventional myosins in muscle 总被引:1,自引:0,他引:1
Redowicz MJ 《European journal of cell biology》2007,86(9):549-558
995.
Conlon JM Al-Dhaheri A Al-Mutawa E Al-Kharrge R Ahmed E Kolodziejek J Nowotny N Nielsen PF Davidson C 《Peptides》2007,28(6):1268-1274
The Cascades frog Rana cascadae belongs to the Amerana (or Rana boylii) group that includes six additional species from western North America (R. aurora, R. boylii, R. draytonii, R. luteiventris, R. muscosa, and R. pretiosa). R. cascadae is particularly susceptible to pathogenic microorganisms in the environment and populations have declined precipitously in parts of its range so that the protection afforded by dermal antimicrobial peptides may be crucial to survival of the species. Peptidomic analysis of norepinephrine-stimulated skin secretions led to the identification of six peptides with differential cytolytic activities that were present in high abundance. Structural characterization showed that they belonged to the ranatuerin-2 (one peptide), brevinin-1 (one peptide), and temporin (four peptides) families. Ranatuerin-2CSa (GILSSFKGVAKGVAKDLAGKLLETLKCKITGC) and brevinin-1CSa (FLPILAGLAAKIVPKLFCLATKKC) showed broad spectrum antibacterial activity (MIC=32microM against Escherichia coli and Staphylococcus aureus) but only brevinin-1CSa was strongly hemolytic against human erythrocytes (LC(50)=5microM). The taxonomy of ranid frogs is currently in a considerable state of flux. The ranatuerin-2 gene is expressed in all members of the Amerana group studied to-date and cladistic analysis based upon a comparison of the amino acid sequences of this peptide indicates that R. cascadae, R. muscosa and R. aurora form a clade that is distinct from one containing R. draytonii, R. boylii, and R. luteiventris. This conclusion is consistent with previous analyses based upon comparisons of the nucleotide sequences of mitochondrial genes. 相似文献
996.
Birkner E Zalejska-Fiolka J Kasperczyk A Kasperczyk S Grucka-Mamczar E Stawiarska-Pieta B Birkner K 《Biological trace element research》2007,120(1-3):179-194
Significant disorders of liver metabolic pathways enzymes after high-cholesterol diet could give information on liver steatosis
development. This process could probably also be inhibited by some compounds, as examined in rabbits. Forty-two male rabbits
were served a high-cholesterol diet (2 g%) (0.67 g/kg b.m./24 h) with addition of d,l-methionine (70 mg/kg b.m./24 h) or seleno-d,l-methionine (12.5 μg/kg b.m./24 h) or α-tocopherol (10 mg/kg b.m./24 h) for 3 months to compare the protection effect of used
compounds on liver metabolism and steatosis. At the beginning and every month, blood was taken. After the experiment was completed,
livers were dissected for histological examinations. The concentration of total cholesterol (t-CH), triacylglycerol (TG),
and the activities of aldolase (ALD), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GLDH), lactate dehydrogenase
(LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were determined. Plasma t-CH and TG concentrations
were significantly higher in all experimental groups vs control group. Blood serum AST and ALT activities did not undergo
change but there were observed not significant increase in the CH group vs control group. Activities of SDH, GLDH, and LDH
increased in blood serum and decreased in the liver in all experimental groups. Activities of LDH and SDH increased in the
liver in the CH+Met group vs CH group. ALD activity decreased in the liver only in the CH and CH+Se groups. This data support
a lipotoxic model of cholesterol-mediated hepatic steatosis. Prolonged administration of high-cholesterol diet not only disturbs
the structure of cell membranes, which is expressed by decreased activity of enzymes in the liver and the migration of those
enzymes to plasma but as well leads to steatosis of the liver, which has been confirmed by histological examinations. The
applied compounds appear to have a varying influence upon the activity of enzymes determined in serum and liver. Obtained
results showed a beneficial influence of methionine and vitamin E supplementation on liver steatosis development. 相似文献
997.
Monika Piro Tomasz Maecki Magda Portas Izabela Magierowska Damian Trojanowski David Sherratt Jolanta Zakrzewska‐Czerwiska Katarzyna Ginda Dagmara Jakimowicz 《Molecular microbiology》2019,111(1):204-220
Although mycobacteria are rod shaped and divide by simple binary fission, their cell cycle exhibits unusual features: unequal cell division producing daughter cells that elongate with different velocities, as well as asymmetric chromosome segregation and positioning throughout the cell cycle. As in other bacteria, mycobacterial chromosomes are segregated by pair of proteins, ParA and ParB. ParA is an ATPase that interacts with nucleoprotein ParB complexes – segrosomes and non‐specifically binds the nucleoid. Uniquely in mycobacteria, ParA interacts with a polar protein DivIVA (Wag31), responsible for asymmetric cell elongation, however the biological role of this interaction remained unknown. We hypothesised that this interaction plays a critical role in coordinating chromosome segregation with cell elongation. Using a set of ParA mutants, we determined that disruption of ParA‐DNA binding enhanced the interaction between ParA and DivIVA, indicating a competition between the nucleoid and DivIVA for ParA binding. Having identified the ParA mutation that disrupts its recruitment to DivIVA, we found that it led to inefficient segrosomes separation and increased the cell elongation rate. Our results suggest that ParA modulates DivIVA activity. Thus, we demonstrate that the ParA‐DivIVA interaction facilitates chromosome segregation and modulates cell elongation. 相似文献
998.
Przemysław Zaręba Jolanta Jaśkowska Paweł Śliwa Grzegorz Satała 《Bioorganic & medicinal chemistry letters》2019,29(16):2236-2242
More than 300 million people are suffering from depression, one of the civilization diseases in the 21st century. Serotonin 5-HT1AR and dopamine D2R play an important role in the treatment and pathogenesis of depression. Moreover, in recent years, the efficacy of dual 5-HT1A/D2 receptors ligands has been demonstrated in the fight against depression. In this work the new bulky arylpiperazine derivatives (LCAP) were synthesized in microwave radiation field. The affinities for the selected serotonin (5-HT1A,5-HT2A,5-HT6,5-HT7) and dopamine (D2) receptors have been evaluated in vitro. Compounds 5.3a, 5.4, 5.1c, 5.3d, 5.2a are promising dual 5-HT1AR/D2R ligands. The SAR analysis were additionally supported with molecular docking studies. 相似文献
999.
1000.
Gassanov N Jankowski M Danalache B Wang D Grygorczyk R Hoppe UC Gutkowska J 《The Journal of biological chemistry》2007,282(15):11255-11265
Despite the existence of a functional arginine vasopressin (AVP) system in the adult heart and evidence that AVP induces myogenesis, its significance in cardiomyogenesis is currently unknown. In the present study, we hypothesized a role for AVP in cardiac differentiation of D3 and lineage-specific embryonic stem (ES) cells expressing green fluorescent protein under the control of atrial natriuretic peptide (Anp) or myosin light chain-2V (Mlc-2V) promoters. Furthermore, we investigated the nitric oxide (NO) involvement in AVP-mediated pathways. AVP exposure increased the number of beating embryoid bodies, fluorescent cells, and expression of Gata-4 and other cardiac genes. V1a and V2 receptors (V1aR and V2R) differentially mediated these effects in transgenic ES cells, and exhibited a distinct developmentally regulated mRNA expression pattern. A NO synthase inhibitor, L-NAME, powerfully antagonized the AVP-induced effects on cardiogenic differentiation, implicating NO signaling in AVP-mediated pathways. Indeed, AVP elevated the mRNA and protein levels of endothelial NO synthase (eNOS) through V2R stimulation. Remarkably, increased beating activity was found in AVP-treated ES cells with down-regulated eNOS expression, indicating the significant involvement of additional pathways in cardiomyogenic effects of AVP. Finally, patch clamp recordings revealed specific AVP-induced changes of action potentials and increased L-type Ca2+ (ICa,L) current densities in differentiated ventricular phenotypes. Thus, AVP promotes cardiomyocyte differentiation of ES cells and involves Gata-4 and NO signaling. AVP-induced action potential prolongation appears likely to be linked to the increased ICa,L current in ventricular cells. In conclusion, this report provides new evidence for the essential role of the AVP system in ES cell-derived cardiomyogenesis. 相似文献