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391.
Malignant transformation of human cells by constitutive expression of platelet-derived growth factor-BB 总被引:3,自引:0,他引:3
Govindarajan B Shah A Cohen C Arnold RS Schechner J Chung J Mercurio AM Alani R Ryu B Fan CY Cuezva JM Martinez M Arbiser JL 《The Journal of biological chemistry》2005,280(14):13936-13943
Platelet-derived growth factors (PDGFs) comprise a family of growth factors strongly implicated in human oncogenesis. A number of human tumors overexpress PDGF family members or have translocations activating PDGF receptors. Whereas the epidemiologic evidence implicating PDGF in human tumors is strong, malignant transformation of human cells by overexpression of PDGF has not been demonstrated. We have previously developed a human cell line by the sequential introduction of large T cells and telomerase, and we have demonstrated that these cells express functionally active PDGF receptor (PDGFR) beta. In order to determine whether growth factor-mediated transformation of human cells could occur, these cells were transduced with a retrovirus encoding PDGF-BB. Constitutive expression of PDGF-BB led to malignant transformation in nude mice. This is the first demonstration of constitutive signaling causing malignant transformation of human cells. Some of the changes that occur because of constitutive growth factor expression can be reversed by the clinically approved tyrosine kinase inhibitor Glivec, whereas other changes are not reversible by tyrosine kinase inhibitors. Our model allows the assessment of epigenetic changes that occur during human carcinogenesis. In addition, these studies provide insight into the clinical failure of tyrosine kinase inhibitors as monotherapy for advanced malignancy. 相似文献
392.
Hussain NK Yamabhai M Bhakar AL Metzler M Ferguson SS Hayden MR McPherson PS Kay BK 《The Journal of biological chemistry》2003,278(31):28823-28830
The epsin N-terminal homology (ENTH) domain is a protein module of approximately 150 amino acids found at the N terminus of a variety of proteins identified in yeast, plants, nematode, frog, and mammals. ENTH domains comprise multiple alpha-helices folded upon each other to form a compact globular structure that has been implicated in interactions with lipids and proteins. In characterizing this evolutionarily conserved domain, we isolated and identified tubulin as an ENTH domain-binding partner. The interaction, which is direct and has a dissociation constant of approximately 1 microm, was observed with ENTH domains of proteins present in various species. Tubulin is co-immunoprecipitated from rat brain extracts with the ENTH domain-containing proteins, epsins 1 and 2, and punctate epsin staining is observed along the microtubule cytoskeleton of dissociated cortical neurons. Consistent with a role in microtubule processes, the over-expression of epsin ENTH domain in PC12 cells stimulates neurite outgrowth. These data demonstrate an evolutionarily conserved property of ENTH domains to interact with tubulin and microtubules. 相似文献
393.
We have previously reported that telomere erosion is the earliest chromatin modification in cells entering the apoptotic pathway. The purpose of this investigation was to determine whether loss of telomeric DNA was involved in inducing mitotic catastrophe and death in Chinese hamster Don cells. Don, a male Chinese hamster-derived cell line which requires daily subculturing to remain diploid, was grown without subculturing for 1-4 days at 37 degrees C and analyzed cytologically. Our results indicated that (1) the frequency of metaphase chromosomes with structural anomalies was significantly higher in 3-day continuously grown cells than in 1-day control cells (8.2% vs 5.7%; P < 0.01), (2) the mitotic index was considerably lower in 3-day continuously grown cells (0.13%) than in control cells (3.64%), (3) cells grown for 3 days continuously showed a higher incidence (7.6%) of endoreduplicated metaphase chromosomes than did control cells (4.9%), (4) 4-day continuously grown Don cells showed significantly smaller amounts of telomeric DNA in interphase nuclei than did control cells, and (5) apoptotic cells were more frequent in 4-day cell cultures (40.6%) than in control cells (4.3%). These results support our earlier observations and contribute additional support for our hypothesis that telomere reduction is the cause of mitotic catastrophe and that cell death in continuously grown Don cells occurs because of the loss of telomeric DNA. 相似文献
394.
395.
Asha GS Indira M 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2004,137(2):109-114
Alcoholics usually suffer from malnutrition and are especially deficient in micronutrients like vitamin C, selenium and Zn. In the present study, combined effects of selenium and ascorbic acid on alcohol-induced hyperlipidemia were studied in guinea pigs. Four groups of male guinea pigs were maintained for 45 days as follows: control (1 mg ascorbate (AA)/100 g body mass/day), ethanol (900 mg ethanol/100 g body mass + 1 mg AA/100 g body mass/day), selenium+ascorbic acid [(25 mg AA + 0.05 mg Se)/100 g body mass/day], ethanol+selenium+ascorbic acid [(25 mg AA + 0.05 mg Se + 900 mg ethanol)/100 g body mass/day]. Co-administration of selenium and ascorbic acid along with alcohol reduced the concentration of all lipids, as also evidenced from the decreased activities of hydroxymethylglutaryl-CoA reductase and enhanced activities of plasma lecithin cholesterol acyl transferase and lipoprotein lipase. Concentrations of bile acids were increased. We conclude that the supplementation of Se and ascorbic acid reduced alcohol induced hyperlipidemia, by decreased synthesis and increased catabolism. 相似文献
396.
We describe a new spontaneous mutation in BALB/c mice that causes abnormal phenotype, such as congenital cataract and microphthalmia. This abnormality was found to be inheritable because offspring with the same abnormality were produced by backcrossing the abnormal male to its normal female parent. Results of various crosses made to determine the mode of inheritance indicated that this abnormality is attributable to mutation of an autosomal recessive gene. Slit lamp examination of the mutant eyes revealed total lenticular opacity, disturbed typical iris pattern, and abnormal pupillary muscle development. Histologic changes in mutant eyes between gestation day 13 and postnatal day 1 indicated various eye and lens abnormalities, including microphthalmia; underdeveloped iris, optic stalk, cornea, and retina; degenerated lens fibers with lost fibrillar structure; and vacuoles of various sizes at the posterior border of the lens. Mild opacity of the lens was found to progress with age and became denser, resembling mature cataract, and occupying the lens completely at the age of six to eight weeks. We, therefore, temporarily designated this abnormality as dense cataract and microphthalmia, with the gene symbol dcm. 相似文献
397.
Augusti KT Arathy SL Asha R Ramakrishanan J Zaira J Lekha V Smitha S Vijayasree VM 《Indian journal of experimental biology》2001,39(8):760-766
Three months feeding of butter fat (BUF) and beef (BF) separately as components of diet at a level of 21% by weight for albino rats, significantly raised their serum and tissue lipids, lipid peroxidation and activities of certain enzymes. BUF was found to be more atherogenic than BF. On incorporation of 5% garlic, amla or onion separately in the above diets, each of them ameliorated the deleterious effects of the animal fats. A higher hyperlipidemic effect of BUF as compared to that of BF may be due to the fact that the ratio of unsaturated to saturated fats is lower for the former (0.56) than for the latter (0.75) and also that the former is richer in cholesterol content than the latter. The order of the curative effects of the vegetables are garlic>amla>onion. The better hypolipidemic effects and correction of elevated levels of certain enzymes shown by garlic and amla may be due to the facts that they contain comparatively better active principles than that found in onions. 相似文献
398.
Recent applications of starch derivatives in nanodrug delivery 总被引:1,自引:0,他引:1
Asha RodriguesMartins Emeje 《Carbohydrate polymers》2012,87(2):987-994
Starch has found use in industries as diverse as food, textiles, cosmetics, plastics, adhesives, paper, and pharmaceuticals. From a pharmaceutical standpoint, starch finds its value in solid-oral dosage forms, where it has been used as a binder, diluent, and disintegrant. However, only recently has the use of starch in nanotechnology started to make significant advances in biomedical applications, including newer drug delivery techniques. There has been a considerable effort to develop biodegradable nanoparticles as effective drug delivery systems. Being cheap, non-toxic, renewable, biodegradable and compatible with many other materials for industrial applications, starch is attracting the interest of drug delivery scientists. We have put together in a short and concise format, recent applications of starch derivatives in the emerging field of nanodrug delivery with the conclusion that a lot still needs to be done. 相似文献
399.
Recursive pathways are broadly defined as those that catalyze a series of reactions such that the key, bond-forming functional group of the substrate is always regenerated in each cycle, allowing for a new cycle of reactions to begin. Recursive carbon-chain elongation pathways in nature produce fatty acids, polyketides, isoprenoids and α-keto acids (αKAs), which all use modular or iterative approaches for chain elongation. Recently, an artificial pathway for αKA elongation has been built that uses an engineered isopropylmalate synthase to recursively condense acetyl-CoA with αKAs. This synthetic approach expands the possibilities for recursive pathways beyond the modular or iterative synthesis of natural products and serves as a case study for understanding the challenges of building recursive pathways from nonrecursive enzymes. There exists the potential to design synthetic recursive pathways far beyond what nature has evolved. 相似文献
400.
M Moorthy P Samuel JV Peter S Vijayakumar D Sekhar VP Verghese I Agarwal PD Moses K Ebenezer OC Abraham K Thomas P Mathews AC Mishra R Lal J Muliyil AM Abraham 《PloS one》2012,7(9):e41507