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   614篇
  免费   39篇
  国内免费   1篇
  2024年   1篇
  2023年   5篇
  2022年   15篇
  2021年   14篇
  2020年   12篇
  2019年   12篇
  2018年   11篇
  2017年   16篇
  2016年   20篇
  2015年   36篇
  2014年   37篇
  2013年   35篇
  2012年   57篇
  2011年   49篇
  2010年   27篇
  2009年   24篇
  2008年   29篇
  2007年   39篇
  2006年   34篇
  2005年   25篇
  2004年   32篇
  2003年   30篇
  2002年   31篇
  2001年   5篇
  2000年   6篇
  1999年   7篇
  1998年   3篇
  1997年   2篇
  1996年   4篇
  1995年   1篇
  1994年   2篇
  1993年   7篇
  1992年   7篇
  1991年   4篇
  1990年   3篇
  1989年   1篇
  1988年   2篇
  1986年   2篇
  1983年   1篇
  1980年   1篇
  1978年   2篇
  1975年   2篇
  1969年   1篇
排序方式: 共有654条查询结果,搜索用时 343 毫秒
91.
Vesicle trafficking regulates epithelial cell migration by remodeling matrix adhesions and delivering signaling molecules to the migrating leading edge. Membrane fusion, which is driven by soluble N-ethylmaleimide-sensitive factor associated receptor (SNARE) proteins, is an essential step of vesicle trafficking. Mammalian SNAREs represent a large group of proteins, but few have been implicated in the regulation of cell migration. Ykt6 is a unique SNARE existing in equilibrium between active membrane-bound and inactive cytoplasmic pools, and mediating vesicle trafficking between different intracellular compartments. The biological functions of this protein remain poorly understood. In the present study, we found that Ykt6 acts as a negative regulator of migration and invasion of human prostate epithelial cells. Furthermore, Ykt6 regulates the integrity of epithelial adherens and tight junctions. The observed anti-migratory activity of Ykt6 is mediated by a unique mechanism involving the expressional upregulation of microRNA 145, which selectively decreases the cellular level of Junctional Adhesion Molecule (JAM) A. This decreased JAM-A expression limits the activity of Rap1 and Rac1 small GTPases, thereby attenuating cell spreading and motility. The described novel functions of Ykt6 could be essential for the regulation of epithelial barriers, epithelial repair, and metastatic dissemination of cancer cells.  相似文献   
92.
We evaluated the effect of lipopolysaccharides from the plant-growth-promoting associative bacterium Azospirillum brasilense Sp245 and from the enteric bacterium Escherichia coli K12 on the morphogenic potential of in vitro-growing somatic calluses of soft spring wheat (Triticum aestivum L. cv. Saratovskaya 29). A genetic model was used that included two near-isogenic lines of T. aestivum L. cv. Saratovskaya 29 with different embryogenic capacities; one of these lines carries the Rht-B1 dwarfing gene, whereas the other lacks it. When added to the nutrient medium, the lipopolysaccharide of A. brasilense Sp245 promoted the formation of calluses with meristematic centers and stimulated the regeneration ability of the cultured tissues in both lines. By contrast, the lipopolysaccharide of the enteric bacterium E. coli K12 barely affected the morphogenetic activity of callus cells and the yield of morphogenic calluses and regenerated plants. These findings indicate that the lipopolysaccharide of the plant-growth-promoting associative bacterium A. brasilense Sp245 specifically enhances the morphogenetic activity of wheat somatic tissues, which increases the efficacy of culturing of genotypes with a relatively low morphogenic potential. The results of the study may contribute to the improvement of the efficacy of plant cell selection and gene engineering and to a better understanding of the mechanisms responsible for plant recognition of lipopolysaccharides of associative bacteria.  相似文献   
93.
Pharmacogenetics is a field aimed at understanding the genetic contribution to inter-patient variability in drug efficacy and toxicity. Treatment of cardiovascular disease is, in most cases, guided by evidence from well-controlled clinical trials. Given the solid scientific basis for the treatment of most cardiovascular diseases, it is common for patients with a given disease to be treated in essentially the same manner. Thus, the clinical trials have been very informative about treating large groups of patients with a given disease, but are slightly less informative about the treatment of individual patients. Pharmacogenetics and pharmacogenomics have the potential of taking the information derived from large clinical trials and further refining it to select the drugs with the greatest likelihood for benefit, and least likelihood for harm, in individual patients, based on their genetic make-up. In this paper, the current literature on cardiovascular pharmacogenetics is emphasised, and how the use of pharmacogenetic/pharmacogenomic information may be particularly useful in the future in the treatment of cardiovascular diseases is also highlighted.  相似文献   
94.
In this study we investigated the effects of insulin-induced hypoglycaemia on tyrosine hydroxylase (TH) protein and TH phosphorylation in the adrenal gland, C1 cell group, locus coeruleus (LC) and midbrain dopaminergic cell groups that are thought to play a role in response to hypoglycaemia and compared the effects of different concentrations of insulin in rats. Insulin (1 and 10 U/kg) treatment caused similar reductions in blood glucose concentration (from 7.5–9 to 2–3 mmol/L); however, plasma adrenaline concentration was increased 20–30 fold in response to 10 U/kg insulin and only 14 fold following 1 U/kg. Time course studies (at 10 U/kg insulin) revealed that in the adrenal gland, Ser31 phosphorylation was increased between 30 and 90 min (4–5 fold), implying that TH was activated to increase catecholamine synthesis in adrenal medulla to replenish the stores. In the brain, Ser19 phosphorylation was limited to certain dopaminergic groups in the midbrain, while Ser31 phosphorylation was increased in most catecholaminergic regions at 60 min (1.3–2 fold), suggesting that Ser31 phosphorylation may be an important mechanism to maintain catecholamine synthesis in the brain. Comparing the effects of 1 and 10 U/kg insulin revealed that Ser31 phosphorylation was increased to similar extent in the adrenal gland and C1 cell group in response to both doses whereas Ser31 and Ser19 phosphorylation were only increased in response to 1 U/kg insulin in LC and in response to 10 U/kg insulin in most midbrain regions. Thus, the adrenal gland and some catecholaminergic brain regions become activated in response to insulin administration and brain catecholamines may be important for initiation of physiological defences against insulin-induced hypoglycaemia.  相似文献   
95.
The kinetic properties of the Mg2+-activated and Mn2+-activated glutamine synthetase (GS) of Azospirillum brasilense in the biosynthetic reaction were studied. The Mg2+-supported and Mn2+-supported GSs in an average state of adenylylation varied in pH optimum, maximum activity, saturation functions for ammonium and glutamate, affinity to substrates, and in the Me2+-ATP ratio required for the optimal enzyme activity. Seventeen other cations were tested for the maintenance of GS activity. The level of the latter and the kinetic behavior of the GS in A.brasilense is suggested to depend essentially on the concentrations of Mg2+, Mn2+ and Co2+, as well as on their ratio  相似文献   
96.
Here we report the discovery of an Early Carboniferous (Late Visean) 3D cephalopod beak displaying significant similarity to the lower beak of Recent coleoids. It was uncovered in a fragmentarily preserved, longiconic shell from the Moorefield Formation in Arkansas, USA. This shell comprises a fractured 29‐mm‐long body chamber having a maximum diameter of ~14 mm and showing an indistinct pro‐ostracum‐like structure. The beak‐bearing shell could easily have been mistaken for a bactritid or orthocerid if it were not for a coleoid‐type, weakly mineralized, evidently organic‐rich shell wall which shows a lamello‐columnar ultrastructure of a bulk of shell wall thickness and plate ultrastructure of thin outer layer. The specimen is assigned to an as‐yet unnamed shelled coleoid of a so far unknown high‐level taxonomic group. A partially exposed, 4.0‐mm‐long portion of the beak is the lower beak in oblique view from its left side. It exhibits fractured anthracite‐like black, apparently originally chitin material, helmet‐like general shape, broad hood with narrow shallow median groove and small notch posteriorly, pronounced pointed, non‐biomineralized upside belt rostrum, high shoulder and about a 90–100 degrees jaw angle. A broad hood and massive rostrum emphasize its similarity to the lower mandible of Recent Vampyroteuthis and signify that its unique, among living coleoids, structure has been existed for at least since Late Visean time (~333 my).  相似文献   
97.
Li‐rich electrode materials of the family x Li2MnO3·(1?x )LiNia Cob Mnc O2 (a + b + c = 1) suffer a voltage fade upon cycling that limits their utilization in commercial batteries despite their extremely high discharge capacity, ≈250 mA h g?1. Li‐rich, 0.35Li2MnO3·0.65LiNi0.35Mn0.45Co0.20O2, is exposed to NH3 at 400 °C, producing materials with improved characteristics: enhanced electrode capacity and a limited average voltage fade during 100 cycles in half cells versus Li. Three main changes caused by NH3 treatment are established. First, a general bulk reduction of Co and Mn is observed via X‐ray photoelectron spectroscopy and X‐ray absorption near edge structure. Next, a structural rearrangement lowers the coordination number of Co? O and Mn? O bonds, as well as formation of a surface spinel‐like structure. Additionally, Li+ removal from the bulk causes the formation of surface LiOH, Li2CO3, and Li2O. These structural and surface changes can enhance the voltage and capacity stability of the Li‐rich material electrodes after moderate NH3 treatment times of 1–2 h.  相似文献   
98.
Abstract. The ultrastructure of the tegument in Paraechinophallus japonicus (Bothriocephalidea: Echinophallidae), a cestode parasite of the bathypelagic fish Psenopsis anomala , was studied using scanning and transmission electron microscopy. Paraechinophallus japonicus lacks a true scolex. Four different types of microtriches have been observed on the tegumental surface of P. japonicus. Capilliform (∼2.3-μm long) and blade-like spiniform (∼1.4-μm long) microtriches are intermingled on the surface of the pseudoscolex. Capilliform microtriches are distinct in possessing a short base and a long electron-lucent cap. The strobila is covered with two types of microtriches, namely filiform (∼2.1-μm long) and tusk-shaped microtriches (≤4.5-μm long). Tusk-shaped microtriches are limited to the posterior border of each proglottid and are characterized by a short and narrow base, and a large and wide, sharply pointed, electron-dense cap. Similar tusk-shaped microtriches were previously found in members of the family Echinophallidae and may represent an autapomorphy of echinophallid cestodes, all of them being parasitic in centrolophid fish. A unified terminology of microthrix parts is proposed.  相似文献   
99.
We studied action of inorganic phosphate (P(i)) on toxic effects of Tl+ in isolated rat liver mitochondria. This is a convenient model to study the toxicity of heavy metals. P(i) markedly retarded contraction of energized mitochondria swollen in the TlNO3 medium and even stronger stimulated swelling and state 4 of succinate-energized mitochondria in the TlNO3 medium. A valinomycin-induced decrease of K+-diffusion potential was also accelerated by Tl+ in the presence of P(i). The mitochondrial permeability transition pore in the medium containing Ca2+, TlNO3, and nitrates of univalent cations was distinctly stimulated by P(i). However, P(i) did not affect both the Tl+-stimulated swelling of nonenergized mitochondria in the TlNO3 medium and swelling of energized mitochondria in the Tl acetate medium. Respiration stimulated by 2,4-dinitrophenol and monoamine oxidase activity of energized mitochondria were not affected by Tl+ regardless of the presence of P(i). We suggested that stimulation by P(i) of toxic action of Tl+ in mitochondria and cells could be due to even greater enhancement of uncoupling of mitochondria as shown by an additional increase of swelling and state 4, and in the greater probability of opening of MPTP in the presence of P(i) and Ca2+.  相似文献   
100.
Formation of a complex between the tyrosine kinases FAK and Src is a key integrin-mediated signaling event implicated in cell motility, survival, and proliferation. Past studies indicate that FAK functions in the complex primarily as a "scaffold," acting to recruit and activate Src within cell/matrix adhesions. To study the cellular impact of FAK-associated Src signaling we developed a novel gain-of-function approach that involves expressing a chimeric protein with the FAK kinase domain replaced by the Src kinase domain. This FAK/Src chimera is subject to adhesion-dependent activation and promotes tyrosine phosphorylation of p130Cas and paxillin to higher steady-state levels than is achieved by wild-type FAK. When expressed in FAK -/- mouse embryo fibroblasts, the FAK/Src chimera resulted in a striking cellular phenotype characterized by unusual large peripheral adhesions, enhanced adhesive strength, and greatly reduced motility. Live cell imaging of the chimera-expressing FAK -/- cells provided evidence that the large peripheral adhesions are associated with a dynamic actin assembly process that is sensitive to a Src-selective inhibitor. These findings suggest that FAK-associated Src kinase activity has the capacity to promote adhesion integrity and actin assembly.  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