全文获取类型
收费全文 | 903篇 |
免费 | 39篇 |
国内免费 | 1篇 |
出版年
2023年 | 3篇 |
2022年 | 6篇 |
2021年 | 24篇 |
2020年 | 15篇 |
2019年 | 13篇 |
2018年 | 22篇 |
2017年 | 21篇 |
2016年 | 24篇 |
2015年 | 39篇 |
2014年 | 63篇 |
2013年 | 76篇 |
2012年 | 61篇 |
2011年 | 61篇 |
2010年 | 53篇 |
2009年 | 25篇 |
2008年 | 44篇 |
2007年 | 47篇 |
2006年 | 47篇 |
2005年 | 41篇 |
2004年 | 42篇 |
2003年 | 30篇 |
2002年 | 30篇 |
2001年 | 15篇 |
2000年 | 14篇 |
1999年 | 12篇 |
1998年 | 6篇 |
1997年 | 9篇 |
1996年 | 9篇 |
1995年 | 7篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 9篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 2篇 |
1979年 | 5篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1969年 | 3篇 |
1930年 | 1篇 |
排序方式: 共有943条查询结果,搜索用时 15 毫秒
41.
Water hyacinth (Eichhornia crassipes (Mart.) Solms.) invaded a eutrophic reservoir receiving domestic sewage near Jaipur (India) during 1975 and gradually developed a complete thick cover over the whole water body during Sept.–Oct. 1978. The physico-chemical characteristics of the water and the phytoplankton composition were studied during Sept. 1977–Sept. 1979 by fortnightly sampling. The changes observed during the second year of study are ascribed to the water hyacinth cover. The important changes were: lowering of water temperature, pH, dissolved oxygen content and nitrate nitrogen, and increase in total alkalinity, free carbon dioxide, chemical oxygen demand, ammonia nitrogen, sulphides, calcium, magnesium and phosphate phosphorus. The changes in the phytoplankton were both qualitative and quantitative. The green algae, particularly the species of Ankistrodesmus, Chlorella, Crucigenia and Selenastrum, increased considerably and replaced the blue-green algae, of which Oscillatoria and Microcystis disappeared totally. The densities of several other taxa changed significantly. 相似文献
42.
The ability of two structurally different ruthenium complexes to interfere with the catalytic activity of topoisomerase II was studied to elucidate their molecular mechanism of action and relative antineoplastic activity. The first complex, [RuCl2(C6H6)(dmso)], could completely inhibit DNA relaxation activity of topoisomerase II and form a drug-induced cleavage complex. This strongly suggests that the drug interferes with topoisomerase II activity by cleavage complex formation. The bi-directional binding of [RuCl2(C6H6)(dmso)] to DNA and topoisomerase II was verified by immunoprecipitation experiments which confirmed the presence of DNA and ruthenium in the cleavage complex. The second complex, Ruthenium Salicylaldoxime, could not inhibit topoisomerase II relaxation activity appreciably and also could not induce cleavage complex formation, though its DNA-binding characteristics and antiproliferation activity were almost comparable to those of [RuCl2(C6H6)(dmso)]. The results suggest that the difference in ligands and their orientation around a metal atom may be responsible for topoisomerase II poisoning by the first complex and not by the second. A probable mechanism is proposed for [RuCl2(C6H6)(dmso)], where the ruthenium atom interacts with DNA and ligands of the metal atom form cross-links with topoisomerase II. This may facilitate the formation of a drug-induced cleavage complex. 相似文献
43.
Kaur T Gopalakrishna P Manogaran PS Pande G 《Molecular and cellular biochemistry》2004,265(1-2):85-95
We have investigated the implications of the rise in membrane cholesterol levels on several in vitro and in vivo properties of polyoma virus transformed rat fibroblasts (PyF), with a special emphasis on alpha5beta1 integrin functions. We show that increased membrane cholesterol causes the PyF cells to change their shape and become more bipolar in appearance. These cells also show significantly higher adhesion to the cell-binding domain of fibronectin, increased localization of alpha5beta1 integrin and talin molecules in focal adhesions and a more robust actin cytoskeleton organization. PyF cells with increased membrane cholesterol show reduced growth in vitro and tumours caused by these cells in nude mice are slow growing. These changes in the growth properties of PyF cells are reversible when the cholesterol levels of PyF cells become normal. Our results suggest that changes in membrane cholesterol levels influence the growth and morphological properties of transformed cells, which can be exploited in controlling the growth of tumours in vivo. 相似文献
44.
Biofouling is one of the concerns in the use of titanium for seawater cooled condensers of power plants. Earlier studies have shown that anodized titanium and its alloys with a thin film of anatase (TiO(2)) on its surface can inhibit attachment of Pseudomonas sp. when illuminated with near-UV light (350 - 380 nm). In the present study, a comparison of the photocatalytic inhibition of microbial attachment on titanium surfaces anodized at different voltages was carried out. Thin films of anatase of varying thickness were produced on titanium grade-2 by anodizing in dilute orthophosphoric acid solution at 30 V, 50 V and 100 V. The photocatalytic efficiency of these anodized surfaces was measured by the methylene blue degradation method. The anodised surfaces were exposed to liquid cultures of Gram-negative Pseudomonas sp., Gram-positive Micrococcus sp. and to a mixed algal culture. Photocatalytic inhibition of microbial attachment was maximum on the titanium surface anodized at 30 V, followed by the surface anodized at 50 V and then at 100 V. The photocatalytic inhibition of microbial attachment was also found to be dependent on the cell wall characteristics of the organism. The Gram-negative Pseudomonas sp. with a lipoproteinaceous outer membrane was the most susceptible to the photocatalytic effect, while the Gram-positive Micrococcus sp. with peptidoglycan cell wall showed moderate susceptibility and the algae with siliceous cell wall showed no susceptibility at all. 相似文献
45.
We consider the efficient initialization of structure and parameters of generalized Gaussian radial basis function (RBF) networks using fuzzy decision trees generated by fuzzy ID3 like induction algorithms. The initialization scheme is based on the proposed functional equivalence property of fuzzy decision trees and generalized Gaussian RBF networks. The resulting RBF network is compact, easy to induce, comprehensible, and has acceptable classification accuracy with stochastic gradient descent learning algorithm. 相似文献
46.
Graham IR Hill VJ Manoharan M Inamati GB Dickson G 《The journal of gene medicine》2004,6(10):1149-1158
BACKGROUND: The activity of synthetic antisense oligonucleotides (splicomers) designed to block pre-mRNA splicing at specific exons has been demonstrated in a number of model systems, including constitutively spliced exons in mouse dystrophin RNA. Splicomer reagents directed to Duchenne muscular dystrophy (DMD) RNAs might thus circumvent nonsense or frame-shifting mutations, leading to therapeutic expression of partially functional dystrophin, as occurs in the milder, allelic (Becker) form of the disease (BMD). METHODS: Functional and hybridisation array screens have been used to select optimised splicomers directed to exon 23 of dystrophin mRNA which carries a nonsense mutation in the mdx mouse. Splicomers were transfected into cultured primary muscle cells, and dystrophin mRNA assessed for exon exclusion. Splicomers were also administered to the muscles of mdx mice. RESULTS: Oligonucleotide array analyses with dystrophin pre-mRNA probes revealed strong and highly specific hybridisation patterns spanning the exon 23/intron 23 boundary, indicating an open secondary structure conformation in this region of the RNA. Functional screening of splicomer arrays by direct analysis of exon 23 RNA splicing in mdx muscle cultures identified a subset of biologically active reagents which target sequence elements associated with the 5' splice site region of dystrophin intron 23; splicomer-mediated exclusion of exon 23 was specific and dose-responsive up to a level exceeding 50% of dystrophin mRNA, and Western blotting demonstrated de novo expression of dystrophin protein at 2-5% of wild-type levels. Direct intramuscular administration of optimised splicomer reagents in vivo resulted in the reappearance of sarcolemmal dystrophin immunoreactivity in > 30% of muscle fibres in the mdx mouse CONCLUSIONS: These results suggest that correctly designed splicomers may have direct therapeutic value in vivo, not only for DMD, but also for a range of other genetic disorders. 相似文献
47.
Corbière C Battu S Liagre B Cardot PJ Beneytout JL 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,808(2):255-262
Apoptosis is one of the most important phenomena of cellular biology. Sedimentation field flow fractionation (SdFFF) has been described as an effective tool for cell separation, respecting integrity and viability. Because SdFFF takes advantage of intrinsic properties of eluted cells (size, density, shape or rigidity), we investigated the capacity of SdFFF in monitoring the early and specific biophysical modifications which occurred during cellular apoptosis induction. Then, we used, as an in vitro cellular apoptosis model, the association between human 1547 osteosarcoma cells and diosgenin, a plant steroid known to induce apoptosis. Four other molecules were studied: hecogenin, tigogenin, staurosporine and MG132. Our results demonstrated a correlation between SdFFF elution profile changes (peak shape modification and retention ratio evolution) and effective apoptosis induction. For the first time, we demonstrated that SdFFF could be used to monitor apoptosis induction as early as 6 h incubation, suggesting different applications such as screening series of molecules to evaluate their ability to induce apoptosis, or sorting apoptotic cells to study apoptosis pathway. 相似文献
48.
Zhou Y Dirksen WP Babu GJ Periasamy M 《American journal of physiology. Heart and circulatory physiology》2003,285(6):H2797-H2803
Genetically altered mice are increasingly used as experimental models. However, ANG II responses in mouse blood vessels have not been well defined. Therefore, the aim of this study was to determine the role of ANG II in regulating major blood vessels in C57/BL6J mice with isometric force measurements. Our results showed that in mouse abdominal aorta ANG II induced a concentration-dependent contraction (EC50 4.6 nM) with a maximum contraction of 75.1 +/- 4.9% at 100 nM compared with that of 60 mM K+. Similarly, femoral artery also exhibited a contractile response of 76.0 +/- 3.4% to the maximum concentration of ANG II (100 nM). In contrast, ANG II (100 nM)-induced contraction was significantly less in carotid artery (24.5 +/- 6.6%) and only minimal (3.5 +/- 0.31%) in thoracic aorta. The nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester and the AT2 antagonist PD-123319 failed to enhance ANG II-induced contractions. However, an AT1 antagonist, losartan (10 microM), completely inhibited ANG II (100 nM) response in abdominal aorta and carotid artery. An AT1 agonist, [Sar1]-ANG II (100 nM), behaved similarly to ANG II (100 nM) in abdominal aorta and carotid artery. RT-PCR analyses showed that mouse thoracic aorta has a significantly lower AT1 mRNA level than abdominal aorta. These results demonstrate that major mouse vessels exhibit differential contractions to ANG II, possibly because of varied AT1 receptor levels. 相似文献
49.
We have recently reported that osteopontin (OPN) induces nuclear factor kappaB (NFkappaB)-mediated promatrix metalloproteinase-2 activation through IkappaBalpha/IKK signaling pathways and that curcumin (diferulolylmethane) down-regulates these pathways (Philip, S., and Kundu, G. C. (2003) J. Biol. Chem. 278, 14487-14497). However, the molecular mechanism by which upstream kinases regulate the OPN-induced NFkappaB activation and urokinase type plasminogen activator (uPA) secretion in human breast cancer cells is not well defined. Here we report that OPN induces the phosphatidylinositol 3'-kinase (PI 3'-kinase) activity and phosphorylation of Akt in highly invasive MDA-MB-231 and low invasive MCF-7 cells. The OPN-induced Akt phosphorylation was inhibited when cells were transfected with a dominant negative mutant of the p85 domain of PI 3-kinase (Deltap85) and enhanced when cells were transfected with an activated form of PI 3-kinase (p110CAAX), indicating that PI 3'-kinase is involved in Akt phosphorylation. OPN enhances the interaction between IkappaBalpha kinase (IKK) and phosphorylated Akt. OPN also induces NFkappaB activation through phosphorylation and degradation of IkappaBalpha by inducing the IKK activity. However, both pharmacological (wortmannin and LY294002) and genetic (Deltap85) inhibitors of PI 3'-kinase inhibited OPN-induced Akt phosphorylation, IKK activity, and NFkappaB activation through phosphorylation and degradation of IkappaBalpha. OPN also enhances uPA secretion, cell motility, and extracellular matrix invasion. Furthermore, cells transfected with Deltap85 or the super-repressor form of IkappaBalpha suppressed the OPN-induced uPA secretion and cell motility, whereas cells transfected with p110CAAX enhanced these effects. Pretreatment of cells with PI 3-kinase inhibitors or NFkappaB inhibitory peptide (SN-50) reduced the OPN-induced uPA secretion, cell motility, and invasion. To our knowledge, this is first report that OPN induces NFkappaB activity and uPA secretion by activating PI 3'-kinase/Akt/IKK-mediated signaling pathways and further demonstrates a functional molecular link between OPN-induced PI 3'-kinase-dependent Akt phosphorylation and NFkappaB-mediated uPA secretion, and all of these ultimately control the motility of breast cancer cells. 相似文献
50.