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71.
72.
The development of new therapeutic leads against leishmaniasis relies primarily on screening of a large number of compounds on multiplication of clinically irrelevant transgenic promastigotes. The advent of the successful in vitro culture of axenic amastigotes allows the development of transgenic axenic amastigotes as a primary screen which can test compounds in a high throughput mode like promastigotes, still representative of the clinically relevant mammalian amastigotes stage. The present study reports the development of luciferase-tagged axenic amastigotes of Leishmania donovani, the causative agent of Indian Kala-azar, for in vitro drug screening. Luciferase expressing promastigotes were transformed to axenic amastigotes at a low pH and high temperature without the loss of luciferase expression. As compared to transgenic promastigotes, the luciferase expressing axenic amastigotes exhibited more sensitivity to antileishmanial drugs, particularly to pentavalent antimony (~2.8-fold) and also to the test compounds. Hence, the developed luciferase expressing axenic amastigotes make an ideal choice for high throughput drug screening for antileishmanial compounds. 相似文献
73.
Fulminant hepatic failure (FHF) is an acute form of hepatic encephalopathy resulting from severe inflammatory or necrotic
liver damage without any previously established liver damage. This develops as a complication due to viral infections, and
drug abuse. FHF also occurs in acute disorders like Reye’s syndrome. Although the exact mechanisms in the etiology of FHF
are not understood, elevated levels of brain ammonia have been consistently reported. Such increased ammonia levels are suggested
to alter neurotransmission signals and impair cerebral energy metabolism due to mitochondrial dysfunctions. In the present
study we have examined the role of cerebral electron transport chain complexes, including complex I, II, III IV, and pyruvate
dehydrogenase in the non-synaptic mitochondria isolated from the cortex of the thioacetamide-induced FHF rats. Further, we
have examined if the structure of mitochondria is altered. The results of the current study demonstrated a decrease in the
activity of the complex I by 31 and 48% at 18 and 24 h respectively after the thioacetamide injection. Similarly, the activity
of electron transport chain complex III was inhibited by 35 and 52% respectively, at 18 and 24 h, respectively. The complex
II and complex IV, on the other hand, revealed unaltered activity. Further the activity of pyruvate dehydrogenase at 18 and
24 h after the induction of FHF was inhibited by 29 and 43%, respectively. Our results also suggest mitochondrial swelling
in FHF induced rats. The inhibition of the respiratory complexes III and I and pyruvate dehydrogenase might lead to the increased
production of free radical resulting in oxidative stress and cerebral energy disturbances thereby leading to mitochondrial
swelling and further contributing to the pathogenesis of FHF. 相似文献
74.
75.
The present study was conducted to determine the culturable bacterial profile from Kestopur canal (Kolkata, India) and analyze their heavy metal tolerance. In addition to daily sewage including solid and soluble wastes, a considerable load of toxic metals are released into this water body from industries, tanneries and agriculture, household as well as health sectors. Screening out microbes from such an environment was done keeping in mind their multifunctional application especially for bioremediation. Heavy metals are major environmental pollutants when present in high concentration in soil and show potential toxic effects on growth and development in plants and animals. Some edible herbs growing in the canal vicinity, and consumed by people, were found to harbour these heavy metals at sub-toxic levels. The bioconcentration factor of these plants being <1 indicates that they probably only absorb but not accumulate heavy metals. All the thirteen Grampositive bacteria isolated from these plants rhizosphere were found to tolerate high concentration of heavy metals like Co, Ni, Pb, Cr, Fe. Phylogenetic analysis of their 16S rDNA genes revealed that they belonged to one main taxonomic group — the Firmicutes. Seven of them were found to be novel with 92–95% sequence homology with known bacterial strains. Further microbiological analyses show that the alkaliphilic Bacillus weihenstephanensis strain IA1 and Exiguobacterium aestuarii strain CE1, with selective antibiotic sensitivity along with high Ni2+ and Cr6+ removal capabilities, respectively, can be prospective candidates for bioremediation. 相似文献
76.
S. Prashant M. Sri Lakshmi Sunita V. L. Sirisha V. Vijaya Bhaskar A. Maruthi Rao M. Lakshmi Narasu P. B. Kavi Kishor 《Plant Cell, Tissue and Organ Culture》2012,108(3):421-436
Promoter sequences of a 795 bp cinnamoyl CoA reductase (LlCCR) and 1,882 bp cinnamyl alcohol dehydrogenase (LlCAD) genes were isolated from Leucaena leucocephala, a leguminous tree species by genome walking, and analysed using bioinformatics tools. This revealed presence of cis-elements such as AC-boxes, XYLAT, WRKY, and MYB binding sites in addition to CAAT and TATA boxes. For functional characterization,
each of LlCCR and LlCAD promoter sequences were fused to β-glucuronidase (GUS) reporter gene, immobilized into pBI101 plasmid, and introduced into tobacco via Agrobacterium tumefaciens strain LBA4404. Histochemical observations of transgenic lines indicated tissue-specific expression of GUS in the vascular
tissues of leaves, stems, and roots. These results demonstrate that GUS expression driven by either LlCCR or LlCAD promoters were involved in lignifying tissues, and more specifically in differentiating xylem cells. This observed tissue-specific
expression driven by either LlCCR or LlCAD promoters is sufficient for reducing the lignin content only in vascular tissues, thus overcoming the risks and challenges
associated with down-regulation of lignin content in whole plants. 相似文献
77.
Kamala Gupta Bhaskar Gupta Bharati Ghosh Dibyendu Narayan Sengupta 《Acta Physiologiae Plantarum》2012,34(1):29-40
Importance of higher polyamines, spermidine, and spermine, in relation to the mechanism and adaptation to combat abiotic stress
has been well established in cereals. Owing to their polycationic nature at physiological pH, polyamines bind strongly to
negative charges in cellular components such as nucleic acids, various proteins, and phospholipids. To study the physiological
role of polyamine during salinity stress, phosphorylation study was carried out in cytosolic soluble protein fraction isolated
from the roots of salt tolerant (Nonabokra) and salt sensitive (M-1-48) rice cultivars treated with none (control), NaCl (150 mM,
16 h), spermidine (1 mM, 16 h) or with abscisic acid (100 μM, 16 h). A calcium independent auto regulatory 42 kDa protein
kinase was found to phosphorylate myelin basic protein and casein but not histone. Interestingly, this was the only protein
to be phosphorylated in root cytosolic fraction during NaCl/abscisic acid/spermidine treatment indicating its importance in
salinity mediated signal transduction. This is the first report of polyamine as well as abscisic acid induced protein kinase
activity in rice root in response to salinity stress. 相似文献
78.
T Bhaskar Kumar Ch Sumanth S Vaishaly M Srinivasa Rao KB Chandra Sekhar CL Meda A Kandale D Rambabu G Rama Krishna C Malla Reddy K Shiva Kumar KV Parsa M Pal 《Bioorganic & medicinal chemistry letters》2012,22(17):5639-5647
Novel polysubstituted pyrroles have been designed and accessed via a one-pot multicomponent reaction followed by Pd-mediated C-C bond forming reactions. All the compounds synthesized were tested for their PDE4B inhibitory properties in vitro and two of them obtained via Heck reaction showed significant inhibition. The docking results suggested that these alkenyl derivatives containing ester moiety interact well with the PDE4B protein in silico where the ester carbonyl oxygen played a key role. The pyrrole framework presented here could be a new template for the identification of small molecule based novel inhibitors of PDE4. The single crystal X-ray data of a representative compound is presented. 相似文献
79.
Santosh S. Chobe Bhaskar S. Dawane Khaled M. Tumbi Prajwal P. Nandekar Abhay T. Sangamwar 《Bioorganic & medicinal chemistry letters》2012,22(24):7566-7572
The DNA molecule is a target for plethora of anticancer and antiviral drugs that forms covalent and non-covalent adducts with major or minor groove of DNA. In present study we synthesized series of novel Pyrazolo [1,5-a]pyrimidine derivatives. The newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, and mass spectral data. The selected compounds were studied for interaction with Calf thymus DNA (CT-DNA) using electronic spectra, viscosity measurement and thermal denaturation studies. Further, molecular interactions were revealed for compound IIIa and IVa by computational methodologies. The preferred mode of ligand binding with double helical DNA as well as preferable DNA groove were explored by molecular docking in different DNA models. 相似文献
80.
Mulakayala N Kandagatla B Ismail Rapolu RK Rao P Mulakayala C Kumar CS Iqbal J Oruganti S 《Bioorganic & medicinal chemistry letters》2012,22(15):5063-5066
A convenient and practical methodology for the synthesis of 2-aryl quinazolin-4(3H)-ones by the condensation of o-aminobenzamides with aromatic aldehydes under mild conditions using catalytic InCl(3) with good yields and high selectivities. This method has been extended for the synthesis of 5-aryl pyrazolo[4,3-d]pyrimidin-7(6H)-ones which have potential applications in medicinal chemistry. Many of these compounds were evaluated for their anti-proliferative properties in vitro against four cancer cell lines and several compounds were found to be active. Further in vitro studies indicated that inhibition of sirtuins could be the possible mechanism of action of these molecules. 相似文献