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991.
陵水暗罗活性成分研究 总被引:8,自引:0,他引:8
从陵水暗罗(polyalthia nemoralis A.etDC)根的乙醇提取物中分离得到五个化合物。经光谱(UV,IR,1H-NMR,13C-NMR,DEPT和MS)解析和化学反应,分别鉴定为暗罗素(zincpolyanemine,PN1),2-巯基吡啶-N-氧化物铜盐(PN2),β-谷甾醇(PN3),β-谷甾醇-β-D-吡喃葡萄糖甙(PN4)和2-巯基吡啶-N-氧化物-2-S-β-D-吡喃葡萄糖甙(PN5),其中PN5为新化合物,PN2为新天然产物。PN1和PN2有较强抗疟、防霉杀菌作用。PN5的抗疟、防霉试验尚在进行中。 相似文献
992.
In aqueous solutions, dalvastatin (1) undergoes epimerization as well as hydrolysis. The transformation of the drug was studied as a function of pH at 25°C in aqueous solutions containing 20% acetonitrile. At all pH values, first-order plots for the conversion are biphasic, indicating rapid equilibration of 1 with its epimer (2) and slower hydrolysis of 1 to the corresponding -hydroxy acid (3). Apparent first-order rate constants for the biexponential equation are given as a function of pH. The alkyl–oxygen cleavage of the lactone ring results in the epimerization of 1 to 2, whereas the acyl–oxygen cleavage results in the hydrolysis of 1 to 3. The epimerization is an SN1 reaction reaching an equilibrium of [l]
eq/[2]
eq = 1.27. The epimerization rate is increased with an increase in the water content of the solvent. The hydrolysis of 1 to 3 is acid and base catalyzed. The hydrolysis is reversible in acidic media and irreversible in neutral and basic media. At pH values greater than 9, the hydrolysis reaction proceeds more rapidly than the epimerization. 相似文献
993.
994.
Disposition in mice of 7-hydroxystaurosporine,a protein kinase inhibitor with antitumor activity 总被引:1,自引:0,他引:1
Donald L. Hill Kathleen F. Tillery Lucy M. Rose Claude F. Posey 《Cancer chemotherapy and pharmacology》1994,35(1):89-92
UCN-01, a hydroxylated derivative of staurosporine, was selected for study because of its promising antitumor activity. For mice dosed intravenously, subcutaneously, or by oral gavage with this compound, the maximum tolerated doses (MTD) were 20, 10, and >100 mg/kg, respectively. UCN-01 was stable in mouse and dog plasma, but in human plasma it was converted to a metabolite in a process not inhibited by standard protease and esterase inhibitors. Following n intravenous dose of 10 mg/kg UCN-01, the half-lives for the initial (t
1/2) and terminal (t
1/2) exponential phases of elimination were 10 and 85 min, respectively; the area under the plasma concentration-time curve (AUC value) was 117 g min ml–1. In mice dosed by oral gavage with 10 mg/kg, the calculated value for the half-life of the elimination phase was 150 min. The AUC value was 15 g min ml–1, giving a value for bioavailability of 13%. After subcutaneous dosing with 10 mg/kg, the calculated values for half-lives for the distribution and elimination phases were 23 and 130 min, respectively; the AUC value was 113 g min ml–1. Since this value is equivalent to that obtained for intravenous dosing, administration of UCN-01 by the subcutaneous route may be an alternative to intravenous dosing in preclinical and clinical trials.This work was supported by contract NO1-CM-27710 (National Cancer Institute, National Institutes of Health, Department of Health and Human Services) 相似文献
995.
Lai-Chen Tsai B.S. Yung-Liang Chen M.S. Chung Lee Ph.D. Horng-Min Chen M.S. Zo-Nan Chang B.S. Mei-Whey Hung B.S. Pei-Ling Chao M.S. Jung-Yaw Lin Ph.D. 《Diseases of the colon and rectum》1995,38(10):1067-1074
PURPOSE: The aim of this study was to assess an immunotoxin, monoclonal antibody C27-abrin A chain conjugate (MAAC), that might be effective in the treatment of colorectal carcinoma. METHODS: The immunotoxin was prepared by a specific monoclonal antibody against carcinoembryonic antigen (CEA), monoclonal antibody C27, linked toN-succinimidyl-3-(2-pyridyldithio)propionate and then coupled covalently to the toxic abrin-A chain to synthesize MAAC. The therapeutic role of this immunotoxin in suppressing thein vitro andin vivo growth of CEA-secreting human colorectal cancer cells (LS174T) was assayed by methods of protein biosynthesis inhibition, cell colony proliferation, and treatment of tumor cells before and after inoculation in nude mice. RESULTS: We found that MAAC effectively suppressed the growth of LS174T in culture medium and completely eradicated cells in inoculated nude mice. In contrast, irrelevant immunotoxin antiferritin-abrin A chain conjugate and isotype-matched monoclonal immunoglobin (MOPC21IgG1)-abrin A chain conjugate did not cause such effects. Thein vitro toxicity was highly specific because the conjugate (MAAC) inhibitedde novo protein biosynthesis, impeded growth, and caused death of cells possessing surface CEA determinants. The 50 percent inhibition dose values of the conjugate for colonogenic survival and for protein biosynthesis in LS174T cells were 0.09 g/ml and 0.06 g/ml, respectively. Colony survival was inhibited 96.3 percent after prolonged MAAC treatment. MAAC showed selective cytotoxicity; the inhibitory effect of MAAC to the CEA-secreting LS174T cells over the CEA-nonsecreting human embryonic kidney cells was 16-fold. CONCLUSION: These results indicate that MAAC may be of benefit in therapy during or soon after resection of colorectal carcinoma or in patients who have micrometastasis.Supported by a grant from the National Science Council and the Veterans General Hospital-Taipei, Taipei, Taiwan. 相似文献
996.
Assay of hexosaminidase A and B enzymes in four cases with developmental regression and cherry red spot on fundus examination
confirmed that three cases had Tay-Sachs disease, and one case had Sandhoff disease. Prenatal diagnosis was carried out by
hexosaminidase enzyme assay in amniotic fluid and cells in one family, and chorionic villus sample in the second family. The
fetus was diagnosed to be unaffected in one, and affected in the other family. Assay of hexosaminidase A and B is useful for
specific diagnosis of GM2 gangliosidosis, and for prenatal diagnosis to reduce the burden of these disorders. 相似文献
997.
A comprehensive survey was carried out to asses the Vitamin A status of pre-school (0–6 yrs.) and school age (6–12 yrs.) children
of socio-economically backward families from slums of Bombay and its suburbs. The Vitamin A, protein, calories and iron from
the rice and dal based diet was found to be below recommended dietary allowances (RDA). Among the 1956 children surveyed 20%
of the children showed low (<20 μg/dl) serum vitamin A levels. 4.8% of the children were suffering from one or the other signs
of Vitamin A deficiency. Rose Bengal stain test (RBST) and conjuctival impression cytology (CIC) indicted the signs of mild
conjuctival xerosis and of early epithelial changes which were correlated with serum vitamin A levels. Serum iron, PCV, Hb
and RBC levels were below normal. The anthropometric measurements of these children were below 50th percentile of Indian Council
of Medical Research (ICMR) standards. Due to lack of proper nutrition, the overall growth of children is either retarded or
not upto the standard levels as was noted in majority of the children. 相似文献
998.
T. Yamada K. Miyazaki N. Koshikawa M. Takahashi H. Akatsu T. Yamamoto 《Acta neuropathologica》1995,89(3):199-203
Gelatinase A is an enzyme capable of cleaving soluble -amyloid protein (AP), and may function as an -secretase to produce secretory forms of amyloid precursor protein. We examined gelatinase A immunoreactivity in the brains and posterior roots of neurologically normal, lacunar stroke, Alzheimer disease (AD), amyotrophic lateral sclerosis, progressive supranuclear palsy and myasthenia gravis cases. The gelatinase A antibody stained only microglial cells in the white matter in all the brain tissues. In AD brain, the reactive microglia located in the center of classical senile plaques, as well as in other microglial cells in the gray matter, showed no immunoreactivity. Gelatinase A in white matter microglial cells may play a role in preventing local deposition of AP. In the posterior root, Schwann cells had positive immunoreactivity. As with other metalloproteases, gelatinase A in Schwann cells may play an antiproliferative role. 相似文献
999.
Intracellular calcium signals triggered by glutamate receptor activation were studied in primary cortical oligodendrocyte lineage cells and in the oligodendrocyte cell line CG-4. Glutamate, kainate, and AMPA (30-300 μM) increased [Ca 2+]i in both types of cells at the stage of oligodendrocyte progenitors (O-2A; GD3+) or pro-oligodendroblasts (04+). The peak amplitude of Ca2+ responses to glutamate receptor agonists was significantly larger in cortical cells. In CG-4 and in cortical cells, the majority (more than 90%) of bipolar GD3+ or multipolar 04+ cells responded to kamate. In all the cells analyzed, kainate was more efficacious than AMPA and glutamate. The percentage of bipolar or multipolar cells responding to glutamate was significantly lower in the CG-4 cell line than in primary cultures. Cellular responses typical of metabotropic glutamate receptor activation were observed in 20% of the cortical O-2A progenitors, but in none of the CG-4 cells. The AMPA-selective antagonist GYKI 52466 blocked kainate-induced Ca2+ responses in cortical O-2A cells. The selective AMPA receptor modulator cyclothiazide (30 μM) greatly potentiated the effects of AMPA (30-100 μM) on [Ca 2+]i in cortical and CG-4 cells. Our findings indicate that Ca2+ responses in cells of the oligodendrocyte lineage are primarily shaped by functional AMPA receptors. © 1995 Wiley-Liss, Inc. 1 This article is a US Government work and, as such, is in the public domain in the United States of America. 相似文献
1000.
Ralph Bültmann Bernd Driessen Jorge Gonçalves Klaus Starke 《Naunyn-Schmiedeberg's archives of pharmacology》1995,351(5):555-560
The effect of Evans blue on nucleotide breakdown, nucleotide-evoked contractions and electrically evoked contractions, overflow of ATP and overflow of tritium (after labelling with [3H]-noradrenaline) was studied in rat vas deferens. Pieces of vas deferens degraded 83 to 85% of added ATP, ADP and 2-methylthio ATP (all 100 M) over 30 min. Evans blue (100 M) reduced this degradation to 22 to 26%. Nucleotides elicited contraction with potency declining in the order , \-methylene ATP > 2-methylthio ATP > ATP > ADP. Evans blue (100 M) shifted the concentration-response curve of , \-methylene ATP to the right and increased the maximum. Concentration-response curves of ATP, ADP and 2-methylthio ATP, in contrast, were shifted to the left and responses were much potentiated. In the presence of Evans blue, the rank order of potency was ATP > 2-methylthio ATP > , \-methylene ATP > ADP. Electrical field stimulation (100 pulses at 10 Hz) elicited contraction and an overflow of tritium and ATP. Evans blue (100 M) did not alter the contraction and the evoked overflow of tritium but increased 24-fold the evoked overflow of ATP. The results indicate that Evans blue may serve as an — albeit impure — ecto-nucleotidase inhibitor in functional experiments. Such experiments demonstrate that the low potency of ATP (and also ADP and 2-methylthio ATP) in eliciting contraction, and the small size of the overflow of ATP upon sympathetic nerve stimulation, are due to rapid breakdown. 相似文献