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981.
982.
In this article, we present a graph theoretic method to visualize and analyze the system behavior under different operating conditions. The system attributes (or variables) are the nodes in the graphs, and partial correlation between a pair of attributes defines the distance between corresponding nodes, resulting in a fully connected graph. Then, the redundant links are reduced using Pathfinder Network Scaling technique to uncover the latent network structure. We use a simulated biological reactor dataset in normal and faulty operation to validate our method. The method is general and can be used to analyze several different systems. 相似文献
983.
Patil Basanagoud S. Vasanthakumar Ganga-Ramu Suresh Babu Vommina V. 《International journal of peptide research and therapeutics》2002,9(4-5):231-233
Summary The Wolff rearrangement of α-diazoketones, derived from Fmoc-α-amino acids, under no base conditions on exposure to microwave
irradiation for 40 to 60 sec to Fmoc-β-amino acids with retention of configuration in good yield (91–95%) is described. 相似文献
984.
Babasaheb P. Bandgar Sachin A. Patil Jalinder V. Totre Balaji L. Korbad Rajesh N. Gacche Baliram S. Hote Shivkumar S. Jalde Hemant V. Chavan 《Bioorganic & medicinal chemistry letters》2010,20(7):2292-2296
A series of nitrogen-containing benzophenone analogues were synthesized by Mannich reaction and evaluated for the inhibition of pro-inflammatory cytokines, TNF-α and IL-6. DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavenging activity and its kinetics were studied to determine the antioxidant potential of the test samples. All the synthesized compounds exhibited promising activity against IL-6 in a range of 81–89%, 09–42% at 10 and 1 μM, respectively, concentration. Exceptionally, the compound 20e was observed to be an effective inhibitor of TNF-α (54%) and IL-6 (97%), (47%) at 10 and 1 μM concentrations with minimum toxicity (22%) against CCK-8 cells. With few exceptions, all other compounds were found to be excellent inhibitors of IL-6 and moderate to excellent inhibitors of TNF-α, however the toxicity profiles of these compounds need to be ameliorated in further optimization studies. Amongst the tested compounds, 16a, 17g, 18f, 18g, 19g and 20e were found to possess significant antioxidant activity. 相似文献
985.
Xiangde Liu Amy Nelson Xingqi Wang Nobuhiro Kanaji Miok Kim Tadashi Sato Masanori Nakanishi YingJi Li Jianhong Sun Joel Michalski Amol Patil Hesham Basma Stephen I. Rennard 《Biochemical and biophysical research communications》2009,380(1):177-38
MicroRNA plays an important role in cell differentiation, proliferation and cell death. The current study found that miRNA-146a was up-regulated in human bronchial epithelial cells (HBECs) in response to stimulation by TGF-ß1 plus cytomix (a mixture of IL-1ß, IFN-γ and TNF-α). TGF-ß1 plus cytomix (TCM) induced apoptosis in HBECs (3.4 ± 0.6% of control vs 83.1 ± 4.0% of TCM treated cells, p < 0.01), and this was significantly blocked by the miRNA-146a mimic (8.8 ± 1.5%, p < 0.01). In contrast, a miRNA-146a inhibitor had only a modest effect on cell survival but appeared to augment the induction of epithelial-mesenchymal transition (EMT) in response to the cytokines. The MicroRNA-146a mimic appears to modulate HBEC survival through a mechanism of up-regulating Bcl-XL and STAT3 phosphorylation, and by this mechanism it could contribute to tissue repair and remodeling. 相似文献
986.
Rooney JP George AD Patil A Begley U Bessette E Zappala MR Huang X Conklin DS Cunningham RP Begley TJ 《Genomics》2009,93(1):42-51
The identification of cellular responses to damage can promote mechanistic insight into stress signalling. We have screened a library of 3968 Escherichia coli gene-deletion mutants to identify 99 gene products that modulate the toxicity of the alkylating agent methyl methanesulfonate (MMS). We have developed an ontology mapping approach to identify functional categories over-represented with MMS-toxicity modulating proteins and demonstrate that, in addition to DNA re-synthesis (replication, recombination, and repair), proteins involved in mRNA processing and translation influence viability after MMS damage. We have also mapped our MMS-toxicity modulating proteins onto an E. coli protein interactome and identified a sub-network consisting of 32 proteins functioning in DNA repair, mRNA processing, and translation. Clustering coefficient analysis identified seven highly connected MMS-toxicity modulating proteins associated with translation and mRNA processing, with the high connectivity suggestive of a coordinated response. Corresponding results from reporter assays support the idea that the SOS response is influenced by activities associated with the mRNA-translation interface. 相似文献
987.
Bagihalli GB Badami PS Patil SA 《Journal of enzyme inhibition and medicinal chemistry》2009,24(2):381-394
A series of metal complexes of cobalt(II), nickel(II) and copper(II) have been synthesized with newly derived biologically active ligands. These ligands were synthesized by the condensation of 3-substituted-4-amino-5-hydrazino-1,2,4-triazole and 8-formyl-7-hydroxy-4-methylcoumarin. The probable structure of the complexes has been proposed on the basis of elemental analyses and spectral (IR, Uv-Vis, magnetic, ESR, FAB-mass and thermal studies) data. Electro chemical study of the complexes is also reported. All these complexes are non-electrolytes in DMF and DMSO. All the ligands and their Co(II), Ni(II) and Cu(II) complexes were screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Staphylococcus pyogenes and Pseudomonas aeruginosa) and antifungal (Aspergillus niger, Aspergillus flavus and cladosporium) activities by MIC method. The brine shrimp bioassay was also carried out to study their in vitro cytotoxic properties. 相似文献
988.
The graft copolymerization of styrene (ST), methyl methacrylate (MMA)/butyl acrylate (BA) with starch was carried chemically using ferrous ion-peroxide redox system. The grafting was performed at 60 °C and the monomer ratios of ST/MMA and ST/BA was varied with their % composition as 80/20, 50/50 and 20/80 parts by weight. The effect of initiator concentration, starch concentration and the monomer ratio on the grafting efficiency was studied. The grafted starch granules (GSG) were further analyzed for their particle size, bulk density and by sizing on cotton yarn for its physico-mechanical properties such as tensile strength, elongation at break, etc. The rheological properties of the resulting granular product in water as well as the starch graft copolymer emulsion were studied. 相似文献
989.
Mangesh R. Bhalekar Varsha Pokharkar Ashwini Madgulkar Nilam Patil Nilkanth Patil 《AAPS PharmSciTech》2009,10(1):289-296
The purpose of this study was to prepare miconazole nitrate (MN) loaded solid lipid nanoparticles (MN-SLN) effective for topical
delivery of miconazole nitrate. Compritol 888 ATO as lipid, propylene glycol (PG) to increase drug solubility in lipid, tween
80, and glyceryl monostearate were used as the surfactants to stabilize SLN dispersion in the SLN preparation using hot homogenization
method. SLN dispersions exhibited average size between 244 and 766 nm. All the dispersions had high entrapment efficiency
ranging from 80% to 100%. The MN-SLN dispersion which showed good stability for a period of 1 month was selected. This MN-SLN
was characterized for particle size, entrapment efficiency, and X-ray diffraction. The penetration of miconazole nitrate from
the gel formulated using selected MN-SLN dispersion as into cadaver skins was evaluated ex-vivo using franz diffusion cell. The results of differential scanning calorimetry (DSC) showed that MN was dispersed in SLN in
an amorphous state. The MN-SLN formulations could significantly increase the accumulative uptake of MN in skin over the marketed
gel and showed a significantly enhanced skin targeting effect. These results indicate that the studied MN-SLN formulation
with skin targeting may be a promising carrier for topical delivery of miconazole nitrate. 相似文献
990.
Sharadrao M. Patil Shihao Xu Sarah R. Sheftic Andrei T. Alexandrescu 《The Journal of biological chemistry》2009,284(18):11982-11991
Amylin is an endocrine hormone that regulates metabolism. In patients
afflicted with type 2 diabetes, amylin is found in fibrillar deposits in the
pancreas. Membranes are thought to facilitate the aggregation of amylin, and
membrane-bound oligomers may be responsible for the islet β-cell toxicity
that develops during type 2 diabetes. To better understand the structural
basis for the interactions between amylin and membranes, we determined the NMR
structure of human amylin bound to SDS micelles. The first four residues in
the structure are constrained to form a hairpin loop by the single disulfide
bond in amylin. The last nine residues near the C terminus are unfolded. The
core of the structure is an α-helix that runs from about residues
5–28. A distortion or kink near residues 18–22 introduces pliancy
in the angle between the N- and C-terminal segments of the α-helix.
Mobility, as determined by 15N relaxation experiments, increases
from the N to the C terminus and is strongly correlated with the accessibility
of the polypeptide to spin probes in the solution phase. The spin probe data
suggest that the segment between residues 5 and 17 is positioned within the
hydrophobic lipid environment, whereas the amyloidogenic segment between
residues 20 and 29 is at the interface between the lipid and solvent. This
orientation may direct the aggregation of amylin on membranes, whereas
coupling between the two segments may mediate the transition to a toxic
structure.Type 2 diabetes affects over 100 million people worldwide
(1) and is thought to cost
upward of $130 billion dollars a year to treat in the United States alone
(2). The endocrine hormone
amylin (also known as islet amyloid polypeptide) appears to have key roles in
diabetes pathology
(3–5).
The normal functions of amylin include the inhibition of glucagon secretion,
slowing down the emptying of the stomach, and inducing a feeling of satiety
through the actions of the hormone on neurons of the hypothalamus in the brain
(5). The effects of amylin are
exerted in concert with those of insulin and reduce the level of glucose in
the blood (3,
5). Circulating amylin levels
increase in a number of pathological conditions, including obesity, syndrome
X, pancreatic cancer, and renal failure
(3). Amylin levels together
with insulin are raised initially in type 2 diabetes but fall as the disease
progresses to a stage where the pancreatic islets of Langerhans β-cells
that synthesize amylin no longer function
(3).One of the hallmarks of type 2 diabetes, found in 90% of patients, is the
formation of extracellular amyloid aggregates composed of amylin
(3–5).
The amyloid deposits accumulate in the interstitial fluid between islet cells
and are usually juxtaposed with the β-cell membranes
(3). Aggregates of amylin are
toxic when added to cultures of β-cells, so that the amyloid found in
situ may be responsible for β-cell death as type 2 diabetes
progresses (6,
7). Genetic evidence that
amylin is directly involved in pathology includes a familial S20G mutation
that leads to early onset of the disease
(8) and produces an amylin
variant that aggregates more readily
(9).As with all amyloids it is unclear whether fibrillar structures or soluble
oligomers are responsible for pathology. A recurrent theme for amyloidogenic
proteins is that toxicity appears to be exerted through membrane-bound
oligomers that form pores and disrupt ion balance across membranes
(4,
10–13).
Experimental evidence for such oligomers has been found for the amyloid-β
(Aβ)2 peptides
(14), which cause Alzheimer
disease, and for α-synuclein (αS), the protein involved in
Parkinson disease (15), a
particular interest of our laboratory. The similar toxic effects exerted by
these amyloidogenic molecules may have a common structural and physical basis.
Detailed structural models are available for Aβ
(16) and αS
(17) bound to SDS micelle
mimetics of membranes. For amylin there are models of peptide fragments
1–19 (18), 20–29
(19), and 17–29
(20) bound to micelles but as
of yet no model of the complete hormone. This turns out to be particularly
important as the interplay between structure and dynamics in amylin only comes
to light when considering the whole molecule.Here we report the solution structure of human amylin bound to SDS
micelles. We complement the structure with information on dynamics and on the
immersion of amylin into micelles. 相似文献