首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1203篇
  免费   102篇
  1305篇
  2023年   4篇
  2022年   10篇
  2021年   21篇
  2020年   6篇
  2019年   10篇
  2018年   19篇
  2017年   16篇
  2016年   29篇
  2015年   44篇
  2014年   54篇
  2013年   71篇
  2012年   116篇
  2011年   79篇
  2010年   59篇
  2009年   65篇
  2008年   92篇
  2007年   71篇
  2006年   94篇
  2005年   73篇
  2004年   66篇
  2003年   67篇
  2002年   64篇
  2001年   15篇
  2000年   11篇
  1999年   18篇
  1998年   23篇
  1997年   17篇
  1996年   7篇
  1995年   11篇
  1994年   3篇
  1993年   6篇
  1992年   7篇
  1991年   8篇
  1990年   10篇
  1989年   2篇
  1988年   3篇
  1986年   5篇
  1985年   4篇
  1984年   4篇
  1983年   3篇
  1980年   2篇
  1979年   1篇
  1978年   2篇
  1977年   1篇
  1975年   2篇
  1974年   3篇
  1972年   1篇
  1971年   1篇
  1970年   1篇
  1969年   2篇
排序方式: 共有1305条查询结果,搜索用时 15 毫秒
31.
An organic-walled dinoflagellate cyst analysis was carried out on 53 surface sediment samples from West Africa (17–6°N) to obtain insight in the relationship between their spatial distribution and hydrological conditions in the upper water column as well as marine productivity in the study area.Multivariate analysis of the dinoflagellate cyst relative abundances and environmental parameters of the water column shows that sea-surface temperature, salinity, marine productivity and bottom water oxygen are the factors that relate significantly to the distribution patterns of individual species in the region.The composition of cyst assemblages and dinoflagellate cyst concentrations allows the identification of four hydrographic regimes; 1) the northern regime between 17 and 14°N characterized by high productivity associated with seasonal coastal upwelling, 2) the southern regime between 12 and 6°N associated with high-nutrient waters influenced by river discharge 3) the intermediate regime between 14 and 12°N influenced mainly by seasonal coastal upwelling additionally associated with fluvial input of terrestrial nutrients and 4) the offshore regime characterized by low chlorophyll-a concentrations in upper waters and high bottom water oxygen concentrations.Our data show that cysts of Polykrikos kofoidii, Selenopemphix quanta, Dubridinium spp., Echinidinium species, cysts of Protoperidinium monospinum and Spiniferites pachydermus are the best proxies to reconstruct the boundary between the NE trade winds and the monsoon winds in the subtropical eastern Atlantic Ocean. The association of Bitectatodinium spongium, Lejeunecysta oliva, Quinquecuspis concreta, Selenopemphix nephroides, Trinovantedinium applanatum can be used to reconstruct past river outflow variations within this region.  相似文献   
32.
Children with phenylketonuria (PKU) have a restricted protein intake and thus low dietary intakes of long-chain polyunsaturated fatty acids (LC-PUFA), which may cause subtle neurological deficits. We measured plasma phospholipid fatty acids and visual evoked potential (VEP) in 36 children with well-controlled PKU (6.3±0.6 years, 19 girls), before and after 3 months of supplementing fish oil capsules providing 15 mg docosahexaenoic acid (DHA)/kg daily. The motometric Rostock-Oseretzky Scale (ROS) was performed before and after supplementation in the 24 PKU children aged >4 years. VEP latencies and ROS were also assessed in omnivorous, age-matched controls without fish oil supply at baseline and after 3 months. Fish oil supply increased plasma phospholipid eicosapentaenoic acid (EPA) (0.40±0.03 vs 3.31±0.19%, p<0.001) and DHA (2.37±0.10 vs 7.05±0.24%, p<0.001), but decreased arachidonic acid (AA) (9.26±0.23 vs 6.76±0.16%, p<0.001). Plasma phenylalanine was unchanged. VEP latencies and ROS results significantly improved after fish oil in PKU children, but remained unchanged in controls. The improvements of VEP latencies, fine motor and coordination skills indicate that preformed n-3 LC-PUFA are needed for neural normalcy in PKU children. The optimal type and dose of supply still needs to be determined. Since PKU children are generally healthy and have normal energy and fatty acid metabolism, these data lead us to conclude that childhood populations in general require preformed n-3 LC-PUFA to achieve optimal neurological function.  相似文献   
33.
34.
Transgenic mice expressing a dominant mutation in the gene for the phototransduction molecule rhodopsin undergo retinal degeneration similar to that experienced by patients with the retinal degenerative disease, retinitis pigmentosa (RP). Although the mutation is thought to cause photoreceptor degeneration in a cell‐autonomous manner, the fact that rod photoreceptor degeneration is slowed in chimeric wild‐type/mutant mice suggests that cellular interactions are also important for maintaining photoreceptor survival. To more fully characterize the nature of the cellular interactions important for rod degeneration in the RP mutant mice, we have used an in vitro approach. We found that when the retinas of the transgenic mice were isolated from the pigmented epithelium and cultured as explants, the rod photoreceptors underwent selective degeneration with a similar time course to that observed in vivo. This selective rod degeneration also occurred when the cells were dissociated and cultured as monolayers. These data indicate that the mutant rod photoreceptors degenerate when removed from their normal cellular relationships and without contact with the pigmented epithelium, thus confirming the relative cell autonomy of the mutant phenotype. We next tested whether normal retinal cells could rescue the mutant photoreceptors in a coculture paradigm. Coculture of transgenic mouse with wild‐type mouse or rat retinal cells significantly enhanced transgenic rod photoreceptor survival; this survival‐promoting activity was diffusible through a filter, was heat labile, and not present in transgenic retinal cells. Several peptide growth factors known to be present in the retina were tested as the potential survival‐promoting molecule responsible for the effects of the conditioned medium; however, none of them promoted survival of the photoreceptors expressing the Pro23His mutant rhodopsin. Nevertheless, we were able to demonstrate that the mutant photoreceptors could be rescued by an antagonist to a retinoic acid receptor, suggesting that the endogeneous survival‐promoting activity may function through this pathway. These data thus confirm and extend the findings of previous work that local trophic interactions are important in regulating rod photoreceptor degeneration in retinitis pigmentosa. A diffusible factor found in normal but not transgenic retinal cells has a protective effect on the survival of rod photoreceptors from Pro23His mutant rhodopsin mice. © 1999 John Wiley & Sons, Inc. J Neurobiol 39: 475–490, 1999  相似文献   
35.

Background  

Carotenoids are plant metabolites which are not only essential in photosynthesis but also important quality factors in determining the pigmentation and aroma of flowers and fruits. To investigate the regulation of carotenoid metabolism, as related to norisoprenoids and other volatile compounds in peach (Prunus persica L. Batsch.), and the role of carotenoid dioxygenases in determining differences in flesh color phenotype and volatile composition, the expression patterns of relevant carotenoid genes and metabolites were studied during fruit development along with volatile compound content. Two contrasted cultivars, the yellow-fleshed 'Redhaven' (RH) and its white-fleshed mutant 'Redhaven Bianca' (RHB) were examined.  相似文献   
36.
Treatment of rheumatoid arthritis (RA) with infliximab (Remicade) has been associated with the induction of antinuclear autoantibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) autoantibodies. In the present study we investigated the humoral immune response induced by infliximab against organ-specific or non-organ-specific antigens not only in RA patients but also in patients with ankylosing spondylitis (AS) during a two-year followup. The association between the presence of autoantibodies and clinical manifestations was then examined. The occurrence of the various autoantibodies was analyzed in 24 RA and 15 AS patients all treated with infliximab and in 30 RA patients receiving methotrexate but not infliximab, using the appropriate methods of detection. Infliximab led to a significant induction of ANA and anti-dsDNA autoantibodies in 86.7% and 57% of RA patients and in 85% and 31% of AS patients, respectively. The incidence of antiphospholipid (aPL) autoantibodies was significantly higher in both RA patients (21%) and AS patients (27%) than in the control group. Most anti-dsDNA and aPL autoantibodies were of IgM isotype and were not associated with infusion side effects, lupus-like manifestations or infectious disease. No other autoantibodies were shown to be induced by the treatment. Our results confirmed the occurrence of ANA and anti-dsDNA autoantibodies and demonstrated that the induction of ANA, anti-dsDNA and aPL autoantibodies is related to infliximab treatment in both RA and AS, with no significant relationship to clinical manifestations.  相似文献   
37.
Gypsy is an endogenous retrovirus present in the genome of Drosophila melanogaster. This element is mobilized only in the progeny of females which contain active gypsy elements and which are homozygous for permissive alleles of a host gene called flamenco (flam). Some data strongly suggest that gypsy elements bearing a diagnostic HindIII site in the central region of the retrovirus body represent a subfamily that appears to be much more active than elements devoid of this site. We have taken advantage of this structural difference to assess by the Southern blotting technique the genomic distribution of active gypsy elements. In some of the laboratory Drosophila stocks tested, active gypsy elements were found to be restricted to the Y chromosome. Further analyses of 14 strains tested for the permissive vs. restrictive status of their flamenco alleles suggest that the presence of permissive alleles of flam in a stock tends to be associated with the confinement of active gypsy elements to the Y chromosome. This might be the result of the female-specific effect of flamenco on gypsy activity. Received: 13 June 1997 / Accepted: 27 August 1997  相似文献   
38.
Little is known about the factors that regulate the production of neurons during the development of the vertebrate central nervous system (CNS); however, evidence from several neuronal cell lines suggests that an increase in intracellular cAMP might trigger the process of differentiation. To determine if a similar process is involved in differentiation during normal CNS neurogenesis, we raised the intracellular level of cAMP in primary cultures of mitotically active, germinal neuroepithelial cells from fetal and postnatal rat retina. This treatment induced differentiation of the CNS precursors, causing the cells to cease DNA synthesis and increase their expression of proteins normally found in differentiated retinal cells. These results indicate that germinal neuroepithelial cell differentiation can be controlled through the cAMP second messenger system, and that the regulation of this system may in part determine the numbers and ratios of the various classes of neurons during the normal development of the CNS.  相似文献   
39.
Summary In vivo localization of a mouse monoclonal antibody (F2-10.23 IgM) binding leukemic L 1210 cells was studied in DBA/2 mice bearing an L 1210 tumor. F(ab)2 fragments were prepared and their specific binding to L 1210 cells was analyzed by flow cytofluorometry. Radiolocalization studies were performed by using 125I- or 131I-labeled IgM monoclonal antibody or its F(ab')2 fragments to ascertain their capacity to visualize the L 1210 tumor. F(ab)2 fragments were cleared more rapidly than the whole IgM; the clearance was as fast in healthy as in tumor-bearing mice. The tumor-to-muscle ratio observed 24 h after injection of 125I-radiolabeled F(ab)2 fragments and 125I-radiolabeled IgM was 10; the radioactivity level in the blood with F(ab)2 fragments was lower than with IgM, and so -camera imaging was workable with F(ab)2 fragments without background substraction. The tumor localization was studied over a period of 5 days by recording the distribution of the iodinated fragments in the tumor-bearing leg compared with that in the normal leg, and by computer analysis of the region of interest. F(ab)2 fragments gave better results than intact IgM in tumor visualization. Nevertheless, the rapid clearance of this antibody or its F(ab)2 fragments make them hardly suitable as carriers of toxic drugs. Abbreviations used are: MEM Minimum essential medium; SDS sodium dodecylsulfate; PAGE polyacrylamide gel electrophoresis  相似文献   
40.
The human M phase phosphoprotein 1 (MPP1), previously identified through a screening of a subset of proteins specifically phosphorylated at the G2/M transition (Matsumoto-Taniura, N., Pirollet, F., Monroe, R., Gerace, L., and Westendorf, J. M. (1996) Mol. Biol. Cell 7, 1455-1469), is characterized as a plus-end-directed kinesin-related protein. Recombinant MPP1 exhibits in vitro microtubule-binding and microtubule-bundling properties as well as microtubule-stimulated ATPase activity. In gliding experiments using polarity-marked microtubules, MPP1 is a slow molecular motor that moves toward the microtubule plus-end at a 0.07 microm/s speed. In cycling cells, MPP1 localizes mainly to the nuclei in interphase. During mitosis, MPP1 is diffuse throughout the cytoplasm in metaphase and subsequently localizes to the midzone to further concentrate on the midbody. MPP1 suppression by RNA interference induces failure of cell division late in cytokinesis. We conclude that MPP1 is a new mitotic molecular motor required for completion of cytokinesis.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号