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991.
The objective of present investigation was to formulate self-microemulsifying drug delivery systems (SMEDDS) of tacrolimus
(FK 506), a poorly water soluble immunosuppressant that exhibits low and erratic bioavailability. Solubility of FK 506 in
various oils, surfactants cosurfactants and buffers was determined. Phase diagrams were constructed at different ratios of
surfactant/cosurfactant (K
m
) to determine microemulsion existence region. The effect of oil content, pH of aqueous phase, dilution, and incorporation
of drug on mean globule size of resulting microemulsions was studied. The optimized SMEDDS formulation was evaluated for in vitro dissolution profile in comparison to pure drug and marketed formulation (Pangraf capsules). The in vivo immunosuppressant activity of FK 506 SMEDDS was evaluated in comparison to Pangraf capsules. Area of o/w microemulsion region in phase diagram was increased with increase in K
m
. The SMEDDS yielded microemulsion with globule size less than 25 nm which was not affected by the pH of dilution medium.
The SMEDDS was robust to dilution and did not show any phase separation and drug precipitation even after 24 h. Optimized
SMEDDS exhibited superior in vitro dissolution profile as compared to pure drug and Pangraf capsules. Furthermore, FK 506 SMEDDS exhibited significantly higher
immunosuppressant activity in mice as compared to Pangraf capsules. 相似文献
992.
Hirohumi Arakawa Machender R. Kandadi Evgeniy Panzhinskiy Kenneth Belmore Ge Deng Ebony Love Preshus M. Robertson Juliette J. Commodore Carolyn J. Cassady Sreejayan Nair John B. Vincent 《Journal of biological inorganic chemistry》2016,21(3):369-381
While trivalent chromium has been shown at high doses to have pharmacological effects improving insulin resistance in rodent models of insulin resistance, the mechanism of action of chromium at a molecular level is not known. The chromium-binding and transport agent low-molecular-weight chromium-binding substance (LMWCr) has been proposed to be the biologically active form of chromium. LMWCr has recently been shown to be comprised of a heptapeptide of the sequence EEEEDGG. The binding of Cr3+ to this heptapeptide has been examined. Mass spectrometric and a variety of spectroscopic studies have shown that multiple chromic ions bind to the peptide in an octahedral fashion through carboxylate groups and potentially small anionic ligands such as oxide and hydroxide. A complex of Cr and the peptide when administered intravenously to mice is able to decrease area under the curve in intravenous glucose tolerance tests. It can also restore insulin-stimulated glucose uptake in myotubes rendered insulin resistant by treating them with a high-glucose media. 相似文献
993.
Stanley Ries Violet Wert N. F. D. O'Leary Muraleedharan Nair 《Plant Growth Regulation》1990,9(3):263-273
The naturally occurring plant growth substance elicited by triacontanol was found to be 9--L(+) adenosine by physical and spectral methods. At picomolar concentrations, 9--L(+) adenosine stimulated growth as determined by dry weight measurements of several plant species. Reaction of adenosine deaminase with adenosine from rice showed that small quantities of 9--L(+) adenosine exist in plants. We believe this is the first report of 9--L(+) adenosine as a natural product. 相似文献
994.
Environmental Isolates of Aeromonas spp. Harboring the cagA-Like Gene of Helicobacter pylori 总被引:1,自引:0,他引:1 下载免费PDF全文
Simanti Datta Asis Khan Ranjan K. Nandy Motiur Rehman Sutapa Sinha Santanu Chattopadhyay Suresh C. Das G. Balakrish Nair 《Applied microbiology》2003,69(7):4291-4295
We investigated the presence of cagA-like gene of Helicobacter pylori in environmental isolates of Aeromonas spp. from different water samples of Calcutta, India, by colony hybridization using a cagA-specific DNA probe and by PCR with cagA-specific primers. Nucleotide sequencing of five PCR products revealed 97 to 98% homology to canonical cagA of H. pylori 26695 as well as to four clinical H. pylori strains from Calcutta. The cagA-like gene of the environmental isolates was unstable in laboratory conditions and tended to be lost upon subculturing. 相似文献
995.
Virus-encoded microRNAs: novel regulators of gene expression 总被引:15,自引:0,他引:15
MicroRNAs (miRNAs) are a class of small RNAs that have recently been recognized as major regulators of gene expression. They influence diverse cellular processes ranging from cellular differentiation, proliferation, apoptosis and metabolism to cancer. Bioinformatic approaches and direct cloning methods have identified >3500 miRNAs, including orthologues from various species. Experiments to identify the targets and potential functions of miRNAs in various species are continuing but the recent discovery of virus-encoded miRNAs indicates that viruses also use this fundamental mode of gene regulation. Virus-encoded miRNAs seem to evolve rapidly and regulate both the viral life cycle and the interaction between viruses and their hosts. 相似文献
996.
Rupak Mitra Pradip K Saha Indira Basu Aparna Venkataraman B.S Ramakrishna M.John Albert Yoshifumi Takeda G.Balakrish Nair 《FEMS microbiology letters》1998,169(2):331-339
The non-membrane-damaging cytotoxin which causes dramatic cell rounding of cultured HeLa cells was purified to homogeneity from a clinical strain (WO5) of non-toxigenic Vibrio cholerae O1 Inaba belonging to the El Tor biotype. The purified protein has a denatured molecular weight of 35 kDa and a native molecular weight of approximately 37 kDa indicating the monomeric nature of the protein. The 15 N-terminal amino acid sequence of non-membrane-damaging cytotoxin showed complete homology to the hemagglutinin protease previously purified and characterized from V. cholerae O1. Purified non-membrane-damaging cytotoxin from V. cholerae O1 was immunologically and biochemically identical to that previously purified from V. cholerae O26. Non-membrane-damaging cytotoxin was found to be enterotoxic in rabbit ileal loop assay inducing accumulation of non-hemorrhagic fluid at 100 μg and elicited a concentration dependent increase in short circuit current and tissue conductance of rabbit ileal mucosa mounted on Ussing chambers. A significant serum immunoglobulin G response against non-membrane-damaging cytotoxin was elicited by patients infected with V. cholerae O139 but not with V. cholerae O1. These properties make non-membrane-damaging cytotoxin a potential virulence factor of V. cholerae which should be taken into consideration while making live, attenuated recombinant vaccine strains against cholera. 相似文献
997.
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1000.
Bae B Cobb RE DeSieno MA Zhao H Nair SK 《The Journal of biological chemistry》2011,286(41):36132-36141
The enzyme FrbF from Streptomyces rubellomurinus has attracted significant attention due to its role in the biosynthesis of the antimalarial phosphonate FR-900098. The enzyme catalyzes acetyl transfer onto the hydroxamate of the FR-900098 precursors cytidine 5'-monophosphate-3-aminopropylphosphonate and cytidine 5'-monophosphate-N-hydroxy-3-aminopropylphosphonate. Despite the established function as a bona fide N-acetyltransferase, FrbF shows no sequence similarity to any member of the GCN5-like N-acetyltransferase (GNAT) superfamily. Here, we present the 2.0 ? resolution crystal structure of FrbF in complex with acetyl-CoA, which demonstrates a unique architecture that is distinct from those of canonical GNAT-like acetyltransferases. We also utilized the co-crystal structure to guide structure-function studies that identified the roles of putative active site residues in the acetyltransferase mechanism. The combined biochemical and structural analyses of FrbF provide insights into this previously uncharacterized family of N-acetyltransferases and also provide a molecular framework toward the production of novel N-acyl derivatives of FR-900098. 相似文献