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681.
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Plasmodium falciparum alanine M1-aminopeptidase (PfA-M1) is a validated target for anti-malarial drug development. Presence of
significant similarity between PfA-M1 and human M1-aminopeptidases, particularly within regions of enzyme active site leads to
problem of non-specificity and off-target binding for known aminopeptidase inhibitors. Molecular docking based in silico screening
approach for off-target binding has high potential but requires 3D-structure of all human M1-aminopeptidaes. Therefore, in the
present study 3D structural models of seven human M1-aminopeptidases were developed. The robustness of docking parameters
and quality of predicted human M1-aminopeptidases structural models was evaluated by stereochemical analysis and docking of
their respective known inhibitors. The docking scores were in agreement with the inhibitory concentrations elucidated in enzyme
assays of respective inhibitor enzyme combinations (r2≈0.70). Further docking analysis of fifteen potential PfA-M1 inhibitors
(virtual screening identified) showed that three compounds had less docking affinity for human M1-aminopeptidases as compared
to PfA-M1. These three identified potential lead compounds can be validated with enzyme assays and used as a scaffold for
designing of new compounds with increased specificity towards PfA-M1. 相似文献
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The hypervariable D-loop region of mitochondrial DNA (mtDNA) was amplified with the polymerase chain reaction using total horse DNA samples. Analysis of single strand conformation polymorphism (SSCP) of denatured amplification products was carried out by native polyacrylamide (8%) gel electrophoresis followed by silver staining. As many as 15 distinct SSCP variants were revealed when screening a total of 78 maternally unrelated horses representing five different breeds. All breeds showed a high degree of polymorphism and the estimated probability (PImt ) that two maternally unrelated individuals have, by chance, identical SSCP variants varied between 0.14 and 0.30. We detected no heteroplasmy or deviations from strict and stable maternal inheritance when examining four maternal lineages, each represented by six to eight horses, separated by up to five generations from a common ancestral mare. The study establishes a simple screening method for detecting equine mtDNA types, which can be applied for tracing maternal genealogies and for association studies. 相似文献
686.
Avinash Kumar Vijay Rani Rajpal Ambika Rachayya Mallikarjun Devarumath Amita Kumari Rakesh Thakur Manju Chaudhary Pradeep Pratap Singh Shiv Murat Singh Chauhan Soom Nath Raina 《Physiology and Molecular Biology of Plants》2021,27(4):727
Picrorhiza kurroa is a medicinally important, high altitude perennial herb, endemic to the Himalayas. It possesses strong hepato-protective bioactivity that is contributed by two iridoid picroside compounds viz Picroside-I (P-I) and Picroside-II (P-II). Commercially, many P. kurroa based hepato-stimulatory Ayurvedic drug brands that use different proportions of P-I and P-II are available in the market. To identify genetically heterozygous and high yielding genotypes for multiplication, sustained use and conservation, it is essential to assess genetic and phytochemical diversity and understand the population structure of P. kurroa. In the present study, isolation and HPLC based quantification of picrosides P-I and P-II and molecular DNA fingerprinting using RAPD, AFLP and ISSR markers have been undertaken in 124 and 91 genotypes, respectively. The analyzed samples were collected from 10 natural P. kurroa Himalayan populations spread across four states (Jammu & Kashmir, Sikkim, Uttarakhand and Himachal Pradesh) of India. Genotypes used in this study covered around 1000 km geographical area of the total Indian Himalayan habitat range of P. kurroa. Significant quantitative variation ranging from 0.01 per cent to 4.15% for P-I, and from 0.01% to 3.18% in P-II picroside was observed in the analyzed samples. Three molecular DNA markers, RAPD (22 primers), ISSR (15 primers) and AFLP (07 primer combinations) also revealed a high level of genetic variation. The percentage polymorphism and effective number of alleles for RAPD, ISSR and AFLP analysis varied from 83.5%, 80.6% and 72.1%; 1.5722, 1.5787 and 1.5665, respectively. Further, the rate of gene flow (Nm) between populations was moderate for RAPD (0.8434), and AFLP (0.9882) and comparatively higher for ISSR (1.6093). Fst values were observed to be 0.56, 0.33, and 0.51 for RAPD, ISSR and AFLP markers, respectively. These values suggest that most of the observed genetic variation resided within populations. Neighbour joining (NJ), principal coordinate analysis (PCoA) and Bayesian based STRUCTURE grouped all the analyzed accessions into largely region-wise clusters and showed some inter-mixing between the populations, indicating the existence of distinct gene pools with limited gene flow/exchange. The present study has revealed a high level of genetic diversity in the analyzed populations. The analysis has resulted in identification of genetically diverse and high picrosides containing P. kurroa genotypes from Sainj, Dayara, Tungnath, Furkia, Parsuthach, Arampatri, Manvarsar, Kedarnath, Thangu and Temza in the Indian Himalayan region. The inferences generated in this study can be used to devise future resource management and conservation strategies in P. kurroa.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12298-021-00972-w. 相似文献
687.
Evidence for the functional coupling of cyclic AMP in MA-10 mouse Leydig tumour cells 总被引:1,自引:0,他引:1
A number of studies have indicated that increased production of steroids can be obtained with doses of tropic hormone which do not result in detectable increases in intracellular cAMP. It has been suggested that this may be a result of compartmentalization or functional coupling of cAMP generated by hormone-receptor interactions to specific steroid producing pathways in the cell. In the present study we have stimulated the MA-10 mouse Leydig tumour cell with hCG, dibutyryl cAMP (dbcAMP) and forskolin to determine if functional coupling of cAMP occurs. Treatment with hCG, dbcAMP and forskolin all resulted in significant increases in the production of progesterone, the major steroid produced in these cells. Stimulation with hCG followed by 2D-PAGE analysis of the proteins resulted in the appearance of two proteins in the 30,000 molecular weight range (pI 6.8 and 6.6) and two in the 25,000-27,000 region (pI 5.9-6.0). Stimulation with dbcAMP or forskolin resulted in the appearance of the same proteins seen with hCG, but also in the appearance of two additional proteins, also having molecular weights of approximately 30,000 (pI 6.3 and 6.1). These data indicate that cAMP generated via hCG stimulation, whilst able to generate similar amounts of progesterone, does not stimulate the synthesis of the same proteins as does cAMP added exogenously or generated through indiscriminate activation of adenylate cyclase activity. Thus, it would appear that the gonadotropin activated pathway generates cAMP which remains functionally compartmentalized within the cell. 相似文献
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Monika Chaudhary Neeraj Kumar Ashish Baldi Ramesh Chandra M. Arockia Babu 《Journal of biomolecular structure & dynamics》2020,38(5):1335-1353
AbstractInspired by the synergistic effects of hetero-aromatic scaffolds on curcumin, a novel array of pyrazoline substituted curcumin analogs was designed. Multi-scale computational studies were carried out to target the proposed analogs on human kinase β (IKK-β), a potential anti-cancer target. In molecular docking analysis, all the eleven molecules were observed to bind the target site and 4-bromo-4’-chloro analog displayed three hydrogen bond interactions with a docking score of –11.534?kcal/mol higher than parent molecule, curcumin (docking score = –7.12?kcal/mol) as the propellant shaped of analogs aided in proper binding with Kinase Domain binding pocket. The molecular dynamics and simulations studies revealed that the stable complexes of lead molecule were developed as the minimal deviations per residue of protein found within the range of 0.11 to 0.92?Å. The proposed compounds were synthesized, characterized and biologically evaluated against human cervical cancer cell line, HeLa, using standard MTT cell assay. Bio-evaluation studies exhibited superior cytotoxic profile for many analogs as Chloro bromo analog with IC50 value (8.7?µg/mL) exhibited fivefolds improvement in the potency in comparison to curcumin (IC50 = 42.4?µg/mL) but was less potent than the standard drug, paclitaxel (IC50 = 0.008µg/mL). The apoptotic effect was evaluated in the terms of caspase-3 enzyme cleavage and exhibited 70.5% of apoptosis significantly (p?<?0.05) higher than 19.9% induced by curcumin. In short, 4-bromo-4’-chloro analog was the potent cytotoxic agent in this structural class and must be evaluated further under a set of stringent parameters for transforming in to a clinically viable therapeutic molecule.Communicated by Ramaswamy H. Sarma 相似文献
690.
Vidhi Chaudhary Radha Prasanna Lata Nain S. C. Dubey Vishal Gupta Rajendra Singh Seema Jaggi Ashok Kumar Bhatnagar 《World journal of microbiology & biotechnology》2012,28(12):3301-3310
Biological control of plant pathogens is receiving increasing relevance, as compared to chemical methods, as they are eco-friendly, economical and indirectly improve plant quality and yield attributes. An investigation was undertaken to evaluate the potential of antagonistic cyanobacteria (Anabaena variabilis RPAN59 and A. oscillarioides RPAN69) fortified formulations for suppressing damping off disease in tomato seedlings challenged by the inoculation of a fungal consortium (Pythium debaryanum, Fusarium oxysporum lycopersici, Fusarium moniliforme and Rhizoctonia solani). Treatment with A. variabilis amended formulations recorded significantly higher plant growth parameters, than other treatments, including biological control (Trichoderma formulation) and chemical control (Thiram-Carbendazim). The A. variabilis amended compost-vermiculite and compost formulations exhibited 10?C15?% lower disease severity and 40?C50?% higher values than chemical and biological control treatments in terms of fresh weight and height of the plants. In future, in depth analyses regarding the mechanism involved in biocontrol by cyanobacteria and evaluation of these formulations under field conditions are proposed to be undertaken. 相似文献