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131.
Pratap S. Jadon Virendra Gajbhiye Rajesh S. Jadon Kavita R. Gajbhiye Narayanan Ganesh 《AAPS PharmSciTech》2009,10(4):1186-1192
The aim of the present report was to develop nonionic surfactant vesicles (niosomes) to improve poor and variable oral bioavailability
of griseofulvin. Niosomes were prepared by using different nonionic surfactants span 20, span 40, and span 60. The lipid mixture
consisted of surfactant, cholesterol, and dicetyl phosphate in the molar ratio of 125:25:1.5, 100:50:1.5, and 75:75:1.5, respectively.
The niosomal formulations were prepared by thin film method and ether injection method. The influence of different formulation
variables such as surfactant type, surfactant concentration, and cholesterol concentration was optimized for size distribution
and entrapment efficiency for both methods. Result indicated that the niosomes prepared by thin film method with span 60 provided
higher entrapment efficiency. The niosomal formulation exhibited significantly retarded in vitro release as compared with free drug. The in vivo study revealed that the niosomal dispersion significantly improved the oral bioavailability of griseofulvin in albino rats
after a single oral dose. The maximum concentration (C
max) achieved in case of niosomal formulation was approximately double (2.98 μg/ml) as compared to free drug (1.54 μg/ml). Plasma
drug profile also suggested that the developed niosomal system also has the potential of maintaining therapeutic level of
griseofulvin for a longer period of time as compared to free griseofulvin. The niosomal formulation showed significant increase
in area under the curve0-24 (AUC; 41.56 μg/ml h) as compared to free griseofulvin (22.36 μg/ml h) reflecting sustained release characteristics. In conclusion,
the niosomal formulation could be one of the promising delivery system for griseofulvin with improved oral bioavailability
and prolonged drug release profiles. 相似文献
132.
Krishan Kumar Megha Tharad Swetha Ganapathy Geeta Ram Azeet Narayan Jameel Ahmad Khan Rana Pratap Anamika Ghosh Sachin Kumar Samuchiwal Sushil Kumar Kuhulika Bhalla Deepti Gupta Krishnamurthy Natarajan Yogendra Singh Anand Ranganathan 《PloS one》2009,4(11)
Background
The secretory proteins of Mycobacterium tuberculosis (M. tuberculosis) have been known to be involved in the virulence, pathogenesis as well as proliferation of the pathogen. Among this set, many proteins have been hypothesized to play a critical role at the genesis of the onset of infection, the primary site of which is invariably the human lung.Methodology/Principal Findings
During our efforts to isolate potential binding partners of key secretory proteins of M. tuberculosis from a human lung protein library, we isolated peptides that strongly bound the virulence determinant protein Esat6. All peptides were less than fifty amino acids in length and the binding was confirmed by in vivo as well as in vitro studies. Curiously, we found all three binders to be unusually rich in phenylalanine, with one of the three peptides a short fragment of the human cytochrome c oxidase-3 (Cox-3). The most accessible of the three binders, named Hcl1, was shown also to bind to the Mycobacterium smegmatis (M. smegmatis) Esat6 homologue. Expression of hcl1 in M. tuberculosis H37Rv led to considerable reduction in growth. Microarray analysis showed that Hcl1 affects a host of key cellular pathways in M. tuberculosis. In a macrophage infection model, the sets expressing hcl1 were shown to clear off M. tuberculosis in much greater numbers than those infected macrophages wherein the M. tuberculosis was not expressing the peptide. Transmission electron microscopy studies of hcl1 expressing M. tuberculosis showed prominent expulsion of cellular material into the matrix, hinting at cell wall damage.Conclusions/Significance
While the debilitating effects of Hcl1 on M. tuberculosis are unrelated and not because of the peptide''s binding to Esat6–as the latter is not an essential protein of M. tuberculosis–nonetheless, further studies with this peptide, as well as a closer inspection of the microarray data may shed important light on the suitability of such small phenylalanine-rich peptides as potential drug-like molecules against this pathogen. 相似文献133.
Sandeep Dave H. Kitdorlang Dkhar Manvendra Pratap Singh Garima Gupta Vemika Chandra Sahil Mahajan Pawan Gupta 《The international journal of biochemistry & cell biology》2010,42(6):938-947
Stem bromelain is a proteolytic phytoprotein with a variety of therapeutic effects. Understanding its structural properties could provide insight into the mechanisms underlying its clinical utility. Stem bromelain was evaluated for its conformational and folding properties at the pH conditions it encounters when administered orally. It exists as a partially folded intermediate at pH 2.0. The conformational changes to this intermediate state were evaluated using fluorinated alcohols known to induce changes similar to those seen in vivo. Studies using circular dichroism, fluorescence emission spectroscopy, binding of the hydrophobic dye 1-anilino-8-naphthalene sulfonic acid and mass spectrometry indicate that treatment with 10–30% hexafluoroisopropanol induces the partially folded intermediate to adopt much of the native protein's secondary structure, but only a rudimentary tertiary structure, characteristic of the molten globule state. Addition of slightly higher concentrations of hexafluoroisopropanol caused transformation from an α-helix to a β-sheet and induced formation of a compact nonnative structure. This nonnative form was more inhibitory of cell survival than either the native or the partially folded intermediate forms, as measured by enhanced suppression of proliferative cues (e.g., extracellular-signal-regulated kinase) and initiation of apoptotic events. The nonnative form also showed better antitumorigenic properties, as evaluated using an induced two-stage mouse skin papilloma model. In contrast, the nonnative state showed only a fraction of the proteolytic activity of the native form. This study demonstrates that hexafluoroisopropanol can induce a conformational change in stem bromelain to a form with potentially useful therapeutic properties different from those of the native protein. 相似文献
134.
135.
Ibne Ali Vikrant Singh Chouhan Satyaveer Singh Dangi Mahesh Gupta Ujjwala Tandiya Iqbal Hyder Vijay Pratap Yadav Rudra Prasanna Panda Vazhoor Babitha Vimla Nagar Arvind Sonwane Firdous Ahmad Khan Bikash Chandra Das Gyanendra Singh Sadhan Bag Mihir Sarkar 《Theriogenology》2014
Recent experiments using expression, immunolocalization, and cell culture approaches have provided leading insights into regulation of luteal angiogenesis by different growth factor systems and its role in the function of corpus luteum (CL) in buffalo. On the contrary, lymphangiogenesis and its regulation in the CL are still poorly understood. The aim of this study was to evaluate the expression and localization of lymphangiogenic factors (vascular endothelial growth factor [VEGF]-C and VEGFD), their receptor (VEGFR3), and lymphatic endothelial marker (LYVE1) in bubaline CL during different stages of the estrous cycle and to investigate functional role of VEGFC and VEGFD in luteal lymphangeogenesis. The mRNA and protein expression of VEGFC, VEGFD, and VEGFR3 was significantly greater in mid and late luteal phases, which correlated well with the expression of LYVE1. The lymphangiogenic factors were localized in luteal cells, exclusively in the cytoplasm. Immunoreactivity of VEGFC was greater during midluteal phase and that of VEGFD was greater during the mid and late luteal phases. Luteal cells were cultured in vitro and treated for different time duration (24, 48, and 72 hours) with VEGFC and VEGFD each at 50, 100, and 150 ng/mL concentration and VEGFC with VEGFD at 100 ng/mL concentration. The temporal increase in LYVE1 mRNA expression was significant (P < 0.05) in VEGFC and VEGFC with VEGFD treatment and no significant change was seen in VEGFD treatment. Thus, it seems likely that VEGFD itself has little role in lymphangiogenesis but along with VEGFC it might have a synergistic effect on VEGFR3 receptors for inducing lymphangiogenesis. In summary, the present study provided evidence that VEGFC and VEGFD, and their receptor VEGFR3, are expressed in bubaline CL and are localized exclusively in the cell cytoplasm, suggesting that these factors have a functional role in lymphangiogenesis of CL in buffalo. 相似文献
136.
137.
Savita Gangwar Vijay Pratap Singh Prabhat Kumar Srivastava Jagat Narayan Maurya 《Acta Physiologiae Plantarum》2011,33(4):1385-1397
Effects of exogenous gibberellic acid (GA; 10 and 100 μM) application on growth, protein and nitrogen contents, ammonium (NH4
+) content, enzymes of nitrogen assimilation and antioxidant system in pea seedlings were investigated under chromium (VI)
phytotoxicity (Cr VI; 50, 100 and 250 μM). Exposure of pea seedlings to Cr and 100 μM GA resulted in decreased seed germination,
fresh and dry weight and length of root and shoot, and protein and nitrogen contents compared to control. Compared to control,
Cr and 100 μM GA led to the significant alteration in nitrogen assimilation in pea. These treatments decreased root and shoot
nitrate reductase (NR), glutamine synthetase (GS) and glutamine 2-oxoglutarate aminotransferase (GOGAT) activities (except
50 μM Cr alone for GOGAT) while glutamate dehydrogenase (GDH) activity and NH4
+ content increased. Compared to control, the root and shoot activities of superoxide dismutase (SOD) and ascorbate peroxidase
(APX) increased (except APX activity at 250 μM Cr + 100 μM GA) while catalase (CAT), glutathione reductase (GR) and dehydroascorbate
reductase (DHAR) activities were decreased (except GR at 100 μM GA alone) following exposure of Cr and 100 μM GA. Total ascorbate
and total glutathione in root and shoot decreased by the treatments of Cr and 100 μM GA while their levels were increased
by the application of 10 μM GA compared to Cr treatments alone. It has been reported that application of 10 μM GA together
with Cr alleviated inhibited levels of growth, nitrogen assimilation and antioxidant system compared to Cr treatments alone.
This study showed that application of 10 μM GA counteracts some of the adverse effects of Cr phytotoxicity with the increased
levels of antioxidants and sustained activities of enzymes of nitrogen assimilation; however, 100 μM GA showed apparently
reverse effect under Cr phytotoxicity. 相似文献
138.
A liquid culture system for shoot proliferation and analysis of pharmaceutically active constituents of Catharanthus roseus (L.) G. Don 总被引:1,自引:0,他引:1
Pratap Kumar Pati Jaspreet Kaur Pritika Singh 《Plant Cell, Tissue and Organ Culture》2011,105(3):299-307
An efficient and cost effective micropropagation protocol using liquid medium was developed for Catharanthus roseus, a commercially important medicinal plant. Comparative analysis of shoot growth and proliferation in liquid Murashige and Skoog (MS) medium supplemented with different concentrations of cytokinins [6-Benzyladenine (BA), Kinetin (KN) and Thidiazuron (TDZ)] was conducted. Better response in terms of shoot proliferation, shoot diameter, number of leaves/shoot, number of branches/shoot, fresh weight and dry weight was observed in a liquid medium vis-à-vis solid medium. A sample of 20 ml of liquid medium supplemented with 5 ??M of BA was optimized for propagation of C. roseus by a liquid culture system. Among various concentrations of auxins tried, 1-Naphthaleneacetic acid (NAA) 5 ??M was found to be the best for root induction. Quantification of pharmaceutically important constituents (vincristine and vinblastine) and total alkaloid content of microshoots grown in solid and liquid medium as well as in vitro raised plants and mother plant was also conducted, hitherto unreported in this high-value medicinal plant. This work further lays the foundations for the shifting of plant production from small to commercial scale. 相似文献
139.
Singh VK Upadhyay P Sinha P Mall AK Jaiswal SK Singh A Ellur RK Biradar S Sundaram RM Singh S Ahmed I Mishra B Singh AK Kole C 《Journal of genetics》2011,90(1):11-19
A set of morphological traits and SSR markers were used to determine the genetic relationship among 12 elite thermosensitive genic male sterile (TGMS) lines developed at three different research institutions of India. Agro-morphological data recorded on 20 morphological traits revealed a wide base of genetic variation and a set of four morphological traits could distinguish most of the TGMS lines. Analysis with 30 SSR markers (20 EST-SSRs and 10 genomic SSRs) revealed 27 markers to be polymorphic, amplifying a total of 83 alleles. Each SSR marker amplified 2-6 alleles with an average of 2.76 alleles per marker and a PIC value varying from 0.54 to 0.96. Cluster analysis based on SSR and morphological data clearly differentiated the lines according to their source of origin. Correlation analysis between morphological and molecular data revealed a very poor association (r = 0.06), which could be attributed to selection pressure, genetic drift, sampling error and unknown relationship among related lines. The SSR markers discriminated the genotypes distinctly and quantified the genetic diversity precisely among the TGMS lines. Data on the yield per plant indicated that the genotypes grouping under a similar cluster showed same heterotic behaviour as compared to the genotypes from different clusters when crossed to similar pollinators. 相似文献
140.
Verrier JD Exo JL Jackson TC Ren J Gillespie DG Dubey RK Kochanek PM Jackson EK 《Journal of neurochemistry》2011,118(6):979-987
Many organs express the extracellular 3',5'-cAMP-adenosine pathway (conversion of extracellular 3',5'-cAMP to 5'-AMP and 5'-AMP to adenosine). Some organs release 2',3'-cAMP (isomer of 3',5'-cAMP) and convert extracellular 2',3'-cAMP to 2'- and 3'-AMP and convert these AMPs to adenosine (extracellular 2',3'-cAMP-adenosine pathway). As astrocytes and microglia are important participants in the response to brain injury and adenosine is an endogenous neuroprotectant, we investigated whether these extracellular cAMP-adenosine pathways exist in these cell types. 2',3'-, 3',5'-cAMP, 5'-, 3'-, and 2'-AMP were incubated with mouse primary astrocytes or primary microglia for 1 h and purine metabolites were measured in the medium by mass spectrometry. There was little evidence of a 3',5'-cAMP-adenosine pathway in either astrocytes or microglia. In contrast, both cell types converted 2',3'-cAMP to 2'- and 3'-AMP (with 2'-AMP being the predominant product). Although both cell types converted 2'- and 3'-AMP to adenosine, microglia were five- and sevenfold, respectively, more efficient than astrocytes in this regard. Inhibitor studies indicated that the conversion of 2',3'-cAMP to 2'-AMP was mediated by a different ecto-enzyme than that involved in the metabolism of 2',3'-cAMP to 3'-AMP and that although CD73 mediates the conversion of 5'-AMP to adenosine, an alternative ecto-enzyme metabolizes 2'- or 3'-AMP to adenosine. 相似文献