全文获取类型
收费全文 | 243篇 |
免费 | 7篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 2篇 |
2019年 | 2篇 |
2017年 | 4篇 |
2015年 | 5篇 |
2014年 | 7篇 |
2013年 | 7篇 |
2012年 | 12篇 |
2011年 | 11篇 |
2010年 | 6篇 |
2009年 | 3篇 |
2008年 | 6篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 5篇 |
2004年 | 5篇 |
2003年 | 8篇 |
2002年 | 7篇 |
2001年 | 6篇 |
2000年 | 10篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 7篇 |
1991年 | 6篇 |
1990年 | 7篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 2篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1970年 | 5篇 |
1969年 | 6篇 |
1968年 | 6篇 |
1967年 | 5篇 |
1966年 | 3篇 |
1965年 | 2篇 |
1964年 | 2篇 |
1961年 | 2篇 |
排序方式: 共有250条查询结果,搜索用时 187 毫秒
1.
Enzymatic and morphological response of the thymus to drugs in normal and zinc-deficient pregnant rats and their fetuses 总被引:1,自引:0,他引:1
In the thymus of normally fed pregnant rats the plasma membrane enzymes dipeptidyl peptidase IV (DPP IV) and alkaline phosphatase (alP) were found in cortical and medullary lymphocytes (thymocytes). Plasma membrane aminopeptidase A (APA) and adenosine monophosphate hydrolysing phosphatase (AMPP) were present in cortical reticular cells. In medullary reticular cells, aminopeptidase M (APM), gamma-glutamyl transferase (GGT), adenosine triphosphate (ATPP) and thiamine pyrophosphate (TPPP) cleaving phosphatases were detected. Medullary reticular cells did not contain APA. Lysosomal DPP I and II, acid phosphatase, acid beta-D-galactosidase, beta-D-N-acetyl-glucosaminidase, beta-D-glucuronidase and non-specific esterases occurred especially in macrophages at the corticomedullary junction. The 21-day-old fetal thymus showed a similar reaction pattern as the maternal organ except for APA which was absent before birth. After treatment of the pregnant rats with valproic acid (VPA), salicylic acid (SA), streptozotocin (ST) and retinoic acid (RA) APA showed an increase in activity in the thymic cortex. In addition, ST and RA induced AMPP, ATPP and TPPP activity in cortical reticular cells up to the same pattern as in medullary reticular cells. After ethanol (ET) administration severe damages occurred. The thymic cortex was free of DPP IV-positive lymphocytes; the medullary reticular cells showed reduced or no GGT and occasionally an increased APM activity. Dexamethasone (DEXA) given to normal or zinc-deficient rats produced the most severe lesions; thymocytes with DPP IV activity were completely absent in the cortex and medulla. In Zn-deficient pregnant rats similar alterations were observed as after ET.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
2.
The formation of elastic fibres was observed in the cultured cells derived from the tunica media and the tunica adventitia of mouse aorta. Bundles of myofilaments with dense bodies were abundantly observed in the cytoplasm of the cultured medial cells, and numerous bundles of microfibrillar components were present in the intercellular spaces. Fine granules of approximately 50 nm in diameter were observed in the bundles of microfibrillar components. It was supposed that these fine granules of elastin fused with each other and formed elastic aggregates and then formed large elastic clumps. Numerous bundles of microfibrillar components were also present in the intercellular spaces of the cultured adventitial cells. Elastic aggregates were scarcely observed in the bundles of microfibrillar components. However, large elastic clumps as observed in the medial cell culture could not be found in the adventitial cell culture. It is suggested that the formation of large elastic clumps might be related to the sheet structures or lamellae of elastic fibres in the tunica media. 相似文献
3.
In high density cultures of mouse fetal lung cells, so-called "mass cultures", development of organoid structures, formation of a basement membrane (BM), and differentiation of pneumocytes type II occur accompanied by synthesis and secretion of lamellar bodies. The relationship between the formation of a BM, on the one hand, and morphogenesis as well as differentiation of pneumocytes type II, on the other hand, has been investigated by use of antibodies against BM components in the lung mass culture. It is shown here that anti-laminin antibodies prevented BM formation, but morphogenesis and pneumocyte differentiation occurred as in untreated cultures. Short-term treatment with the antibody revealed that the BM is formed only during the first 2 to 3 days in vitro. Already formed BM could not be removed by anti-laminin. Anti-collagen type IV antibodies showed no effect in the lung mass culture except for a stronger staining of the BM. Anti-BM-1 antibodies caused no changes in morphogenesis, cell differentiation and BM formation either, but the mesenchymal intercellular space exhibited a dark staining, which is probably due to antigen-antibody complexes. The results obtained with anti-laminin antibodies indicate that a BM is not necessary for lung cell differentiation in vitro. 相似文献
4.
Uptake and nature of the intracellular binding of cyclosporin A in a murine thymoma cell line, BW5147 总被引:1,自引:0,他引:1
In a survey of malignant cell lines including a variety of leukemias and lymphomas, BW5147, a T lymphoma from the spontaneous virus-associated thymoma in AKR mice, was found to be the most sensitive to growth inhibition by cyclosporin A (Cs A). Inhibition of growth was cell cycle phase-independent and inhibition of macromolecular precursor uptake was relatively nonspecific. Uptake of radiolabeled Cs A by these cells was characterized by two components: one that appeared saturable at low drug concentrations (0.03 to 1.0 microgram/ml), and another that was nonsaturable at higher drug concentrations (1.0 microgram/ml or higher). Most of the drug concentrated by cells (70 to 80%) was located in the cytosol (100,000 X G supernatant of lysed cells). The apparent m.w. of the drug-macromolecule complex was 15,000 to 20,000 as determined by m.w. exclusion columns. This complex could also be formed by adding drug to cytosol prepared from unexposed cells. The low m.w. complex migrated on a preparative isoelectric focusing column to form two peaks with isoelectric points of 6.8 and 8.5. A method was developed to assay for the binding component, and a sequence of m.w. exclusion columns and isoelectric focusing was used to effect partial purification of the Cs A binding component. 相似文献
5.
Zusammenfassung An einer Reihe von normalen und pathologisch veränderten Organen wird die Porenstruktur, Porenbildung und Porenrückbildung elektronenmikroskopisch untersucht. Die Endothelpore ist eine Diskontinuität in der Endothelwand mit einem sehr konstanten Durchmesser von 500 Å. Das Diaphragma ist nur mit der äußeren Membranlamelle am Porenrand verbunden. Diaphragmalose Poren sind etwas größer (Ø650 Å), zeigen einen glatten Porenrand und kommen besonders in verdichteten Endothelteilen vor. Frustrane Poren münden blind in Vakuolen oder liegen in porösen Endothelfalten im Gefäßlumen. Die eigentliche Bildung der Poren geschieht immer in abgeflachten ( 800 Å) Endothelteilen. Die vorbereitende Abflachung geht jedoch in den verschiedenen Endothelzonen (Periksryon, dicker Endothelwand, Cytoplasmainseln) unterschiedliche Wege. Alle diese Vorgänge stellen Vesikulation in besonderer Lage und mit besonderer Fusionsrichtung der Vesikel dar. Wegen dieser Unterschiede wird die Endothelwand in 4 Zonen eingeteilt: Perikaryon; dicke, porenlose Wandteile mit cytoplasmatischen Vesikeln; dünne, porenhaltige Teile ohne Zellorganellen; dicke Cytoplasmainseln, die die porösen Wandteile voneinander trennen. Der Vorgang der Porenrückbildung bleibt unklar. Vielleicht besteht er in der Faltung des Endothels, die zu porösen Vakuolen führt. Die Porenbildung verändert die Endotheloberfläche nicht, kann aber das Cytoplasmavolumen vermindern. Der Aufbau des Diaphragmas sowie der Mechanismus und die auslösenden Faktoren der Porenbildung werden diskutiert.
Mit Unterstützung durch die Deutsche Forschungsgemeinschaft 相似文献
Summary Ultrastructure, formation and disappearance of endothelial pores was studied electron microscopically in several normal or experimentally changed organs. Pores being discontinuies in the endothelial wall have a very constant diameter of 500 Å. The diaphragm at the margin of the pore is in contact with only the outer lamella of the unit membrane. Pores without a diaphragm being somewhat larger (Ø 650 Å) show a smoother margin and are to be found in endothelia with dense cytoplasm. Frustrated pores form blind openings in vacuoles or are situated in porous endothelial folds within the vessel lumen. Pores alway are formed in flattened parts of endothelium ( 800 Å). In thick capillary walls the endothelium previously is flattened by vesiculation, which differs in different zones of the wall (Perikaryon, thick continuous endothelium, and cytoplasmic islands in porous capillaries) in location and direction of vesicle fusion. Because of these differences the endothelial wall is divided in 4 zones: Perikaryon; thick parts without pores containing cytoplasmic vesicles etc.; flattened, porous parts containing no cytoplasmic organelles; thick cytoplasmic islands which separate porous parts. The process removing pores is not clear. Perhaps they are removed by folding of the endothelial surface and formation porous vacuoles. Formation of pores dosn't enlarge or reduce the surface, but may reduce the cytoplasmic volume of endothelium. The nature of diaphragm as well as the mechanism and releasing factors of the formation of pores are discussed.
Mit Unterstützung durch die Deutsche Forschungsgemeinschaft 相似文献
6.
Zusammenfassung 1. Die Behandlung der nativen und formolfixierten Sehnenfibrillen mit einer ammoniakalischen Silberlösung führt immer zu einer Einlagerung von Silberpartikeln in den D-Teilen der Fibrillen.2. Bei den nativen Fibrillen liegen die Silberkörner in einem, zwei oder drei Streifen im D-Teil.3. In den formolfixierten Fibrillen ist das Silber nur in einem Streifen vorhanden.4. Die Behandlung der nativen und formolfixierten Sehnenfibrillen mit anderen Silbersalzen führt zu keiner Versilberung der Fibrillen.5. Die Behandlung der nativen Sehnenfibrillen mit neutraler Kochsalzlösung oder Trypsin und anschließender Versilberung führt zu keiner wesentlichen Änderung des Silberbildes.6. Hyaluronidase-, Citratpuffer- und Perjodateinwirkung auf native Sehnenfibrillen mit anschließender Versilberung führt zu keiner Innenversilberung der D-Teile.7. Acetylierung und Behandlung mit Bisulfit der nativen Fibrillen und anschließender Versilberung mit ammoniakalischer Silberlösung verhindert eine Innenversilberung der D-Teile.8. Die formolfixierten Fibrillen zeigen eine Innenversilberung der D-Teile nach einer Vorbehandlung mit einer neutralen Kochsalzlösung, Citratpuffer, Hyaluronidase, Trypsin und Perjodat. Nur die Acetylierung und die Behandlung mit Bisulfit verhindert eine Innenversilberung.9. Die Innenversilberung der Sehnenfibrillen durch eine ammoniakalische Silberlösung wird weder durch Licht noch durch Chloride oder lichtempfindliche Silbereiweißverbindungen hervorgerufen.10. Die Versilberung in den D-Teilen wird durch Stoffe in den Fibrillen bewirkt, die Silber aus einer ammoniakalischen Silberlösung ausfällen können.11. Die reduzierenden Stoffe haben enge Beziehungen zur citratlöslichen Fraktion und sind perjodat- und hyaluronidaseempfindlich. Formalinfixierung beeinflußt diesen Versilberungsmodus durch ein vermehrtes Auftreten von Querbindungen.12. Die Sonderstellung der ammoniakalischen Silberlösung für die Innenversilberung wird diskutiert. Sie kann stereochemische Gründe haben oder durch die große Beständigkeitskonstante erklärt werden.13. Das Ausfallen von metallischem Silber in den D-Teilen der Sehnenfibrillen kann nicht mit dem photographischen Prozeß in Verbindung gebracht werden. Das gilt auch für die Bindegewebsversilberung nachGömöri.14. Die Silberorte in den D-Teilen lassen sich nur teilweise mit den bekannten Querstreifungsbildern nach Osmium- oder Phosphorwolframsäurefixierung in Beziehung setzen.
Mit 6 Textabbildungen
Durchgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft. 相似文献
Summary 1. After treatment of native or formalin-fixed tendon fibrils with an ammoniacal silver solution, silver particles are deposited in the D-bands of the fibrils. In the native fibrils these are arranged in one, two or three striae per band, but after formalin fixation they lie in one stria only.2. No external reducing agent is necessary for the production of the particles.3. Pretreatment of native fibrils with neutral salt solution or with trypsin has no effect on subsequent silvering. On the other hand, silvering is abolished by treatment with hyaluronidase, citrate buffer or periodate and also by acetylation and bisulphite.4. Formalin-fixed fibrils show the silvering effect after all these procedures except acetylation or bisulphite treatment.5. It is postulated that silvering of the D-bands is due to reducing substances which can precipitate silver from ammonical solutions and that formalin influences the process by the production of cross linkages.
Mit 6 Textabbildungen
Durchgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft. 相似文献
7.
Anonymous nuclear DNA markers in the American oyster and their implications for the heterozygote deficiency phenomenon in marine bivalves 总被引:4,自引:0,他引:4
A puzzling population-genetic phenomenon widely reported in allozyme
surveys of marine bivalves is the occurrence of heterozygote deficits
relative to Hardy-Weinberg expectations. Possible explanations for this
pattern are categorized with respect to whether the effects should be
confined to protein-level assays or are genomically pervasive and expected
to be registered in both protein- and DNA-level assays. Anonymous nuclear
DNA markers from the American oyster were employed to reexamine the
phenomenon. In assays based on the polymerase chain reaction (PCR), two
DNA-level processes were encountered that can lead to artifactual genotypic
scorings: (a) differential amplification of alleles at a target locus and
(b) amplification from multiple paralogous loci. We describe symptoms of
these complications and prescribe methods that should generally help to
ameliorate them. When artifactual scorings at two anonymous DNA loci in the
American oyster were corrected, Hardy-Weinberg deviations registered in
preliminary population assays decreased to nonsignificant values.
Implications of these findings for the heterozygote-deficit phenomenon in
marine bivalves, and for the general development and use of PCR-based
assays, are discussed.
相似文献
8.
Marta Clariano Vanda Marques João Vaz Salma Awam Marta B. Afonso Maria Jesus Perry Cecília MP Rodrigues 《化学与生物多样性》2023,20(3):e202300222
Curcumin has a plethora of biological properties, making this compound potentially effective in the treatment of several diseases, including cancer. However, curcumin clinical use is compromised by its poor pharmacokinetics, being crucial to find novel analogs with better pharmacokinetic and pharmacological properties. Here, we aimed to evaluate the stability, bioavailability and pharmacokinetic profiles of monocarbonyl analogs of curcumin. A small library of monocarbonyl analogs of curcumin 1a–q was synthesized. Lipophilicity and stability in physiological conditions were both assessed by HPLC-UV, while two different methods assessed the electrophilic character of each compound monitored by NMR and by UV-spectroscopy. The potential therapeutic effect of the analogs 1a–q was evaluated in human colon carcinoma cells and toxicity in immortalized hepatocytes. Our results showed that the curcumin analog 1e is a promising agent against colorectal cancer, with improved stability and efficacy/safety profile. 相似文献
9.
Sampling properties of DNA sequence data in phylogenetic analysis 总被引:26,自引:6,他引:20
We inferred phylogenetic trees from individual genes and random samples of
nucleotides from the mitochondrial genomes of 10 vertebrates and compared
the results to those obtained by analyzing the whole genomes. Individual
genes are poor samples in that they infrequently lead to the whole-genome
tree. A large number of nucleotide sites is needed to exactly determine the
whole-genome tree. A relatively small number of sites, however, often
results in a tree close to the whole-genome tree. We found that blocks of
contiguous sites were less likely to lead to the whole-genome tree than
samples composed of sites drawn individually from throughout the genome.
Samples of contiguous sites are not representative of the entire genome, a
condition that violates a basic assumption of the bootstrap method as it is
applied in phylogenetic studies.
相似文献
10.
The antiepileptic drug valproic acid (VPA) has been implicated as a human teratogen causing spina bifida aperta. Recently, we developed a mouse model inducing spina bifida aperta with VPA. To elucidate the pathogenesis of VPA-induced spina bifida aperta we now investigated the anatomy and histology of this defect in the mouse. The morphology of spina bifida aperta induced by all-trans-retinoic acid (RA) was used for comparison. Various doses of VPA and RA were administered at different times to determine the periods of sensitivity for inducing spina bifida aperta with these drugs. Each administration regimen consisted of three doses applied at intervals of 6 hr. RA induced spina bifida aperta during an earlier developmental period (day 8 of gestation) than VPA (day 9 of gestation). The most effective regimens for induction of spina bifida aperta in mice were injections of 3 x 500 mg VPA-Na/kg body weight (b.w.) intraperitoneally on day 9 of gestation at 0, 6, and 12 hr; RA (12.5 mg/kg b.w.) was given orally on day 8 of gestation at 12 and 18 hr, day 9 at 0 hr. VPA did not induce spina bifida aperta on day 8 of gestation and RA did not induce this effect on day 9 of gestation. Histological studies of day 18 fetuses carrying spina bifida aperta were performed. The spina bifida aperta induced by VPA shows a disorganized and necrotic spinal cord. In the vertebral canal were observed cell debris, blood cells, capillaries, macrophages, and rests of meninges. These results indicate that the spinal cord is almost destroyed at the affected section. In contrast, the spina bifida aperta induced by RA demonstrates a spinal cord organized in the gray and white matter, the dorsal and ventral horn. But the neural canal does not exist, only a layer of ependymal cells lies on the surface of the spinal cord. Our results indicate that the morphology of spina bifida aperta induced by VPA differed distinctly from that induced by RA in the mouse fetus. Moreover VPA produced a spina bifida aperta with a specific morphology. Also the period of sensitivity for induction of this lesion differed and occurred earlier for RA than for VPA. VPA and RA may possibly induce spina bifida aperta via different mechanisms in the mouse. 相似文献