全文获取类型
收费全文 | 1950篇 |
免费 | 134篇 |
国内免费 | 4篇 |
出版年
2023年 | 17篇 |
2022年 | 40篇 |
2021年 | 44篇 |
2020年 | 22篇 |
2019年 | 35篇 |
2018年 | 57篇 |
2017年 | 38篇 |
2016年 | 52篇 |
2015年 | 76篇 |
2014年 | 108篇 |
2013年 | 138篇 |
2012年 | 169篇 |
2011年 | 161篇 |
2010年 | 108篇 |
2009年 | 87篇 |
2008年 | 121篇 |
2007年 | 140篇 |
2006年 | 104篇 |
2005年 | 124篇 |
2004年 | 105篇 |
2003年 | 92篇 |
2002年 | 90篇 |
2001年 | 11篇 |
2000年 | 7篇 |
1999年 | 16篇 |
1998年 | 20篇 |
1997年 | 18篇 |
1996年 | 17篇 |
1995年 | 11篇 |
1994年 | 11篇 |
1993年 | 6篇 |
1992年 | 8篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1978年 | 4篇 |
1976年 | 2篇 |
1969年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有2088条查询结果,搜索用时 31 毫秒
81.
82.
Wilson disease: not just a copper disorder. Analysis of a Wilson disease model demonstrates the link between copper and lipid metabolism 总被引:1,自引:0,他引:1
Copper is an essential nutrient required for normal growth and development in many organisms. In humans, the disruption of normal copper absorption and excretion is associated with two severe disorders, known as Menkes disease and Wilson disease, respectively. The consequences of insufficient copper supply that is characteristic of Menkes disease have been largely linked to the inactivation of key metabolic enzymes, although other non-enzymatic processes may also be involved. In contrast, the consequences of copper accumulation in Wilson disease have been generally ascribed to copper-induced radical-mediated damage. Recent studies suggest that the cellular response to copper overload, particularly at the early stages of copper accumulation, involves more specific mechanisms and specific pathways. Genetic and metabolic characterization of animal models of Wilson disease has provided new insights into the pre-symptomatic effects of copper that is accumulated in the liver. The studies have uncovered unexpected links between copper metabolism, cell-cycle machinery, and cholesterol biosynthesis. We discuss these new findings along with the earlier reports on dietary effects of copper. Together these experiments suggest a tight link between lipid and copper metabolism and identify several candidate proteins that may mediate the cross-talk between copper status and lipid metabolism. 相似文献
83.
84.
Nicholas Mikolajewicz Simon Sehayek Paul W. Wiseman Svetlana V. Komarova 《Biophysical journal》2019,116(10):2009-2022
The skeleton constantly interacts and adapts to the physical world. We have previously reported that physiologically relevant mechanical forces lead to small repairable membrane injuries in bone-forming osteoblasts, resulting in release of ATP and stimulation of purinergic (P2) calcium responses in neighboring cells. The goal of this study was to develop a theoretical model describing injury-related ATP and ADP release, their extracellular diffusion and degradation, and purinergic responses in neighboring cells. After validation using experimental data for intracellular free calcium elevations, ATP, and vesicular release after mechanical stimulation of a single osteoblast, the model was scaled to a tissue-level injury to investigate how purinergic signaling communicates information about injuries with varying geometries. We found that total ATP released, peak extracellular ATP concentration, and the ADP-mediated signaling component contributed complementary information regarding the mechanical stimulation event. The total amount of ATP released governed spatial factors, such as the maximal distance from the injury at which purinergic responses were stimulated. The peak ATP concentration reflected the severity of an individual cell injury, allowing to discriminate between minor and severe injuries that released similar amounts of ATP because of differences in injury repair, and determined temporal aspects of the response, such as signal propagation velocity. ADP-mediated signaling became relevant only in larger tissue-level injuries, conveying information about the distance to the injury site and its geometry. Thus, we identified specific features of extracellular ATP and ADP spatiotemporal signals that depend on tissue mechanoresilience and encode the severity, scope, and proximity of the mechanical stimulus. 相似文献
85.
Grabeklis Andrey R. Skalny Anatoly V. Skalnaya Anastasia A. Zhegalova Irina V. Notova Svetlana V. Mazaletskaya Anna L. Skalnaya Margarita G. Tinkov Alexey A. 《Biological trace element research》2019,187(1):230-242
Biological Trace Element Research - Chronic exposure to lead causes disruption to energy production mechanisms and tissue damage, in particular through its binding to thiol groups and competition... 相似文献
86.
F. William Sunderman Alison H. Varghese Olga S. Kroftova Svetlana Grbacivankovic Jaromir Kotyza Arun K. Datta Milton Davis Wojciech Bal Kazimierz S. Kasprzak 《Molecular reproduction and development》1996,44(4):507-524
A Ni(II)-binding serpin, pNiXA, is abundant in Xenopus oocytes and embryos. Kinetic assays show that purified pNiXa strongly inhibits bovine α-chymotrypsin (K1 = 3 mM), weakly inhibits porcine elastase (K1 = 0.5 μM), and does not inhibit bovine trypsin. The reversible, slow-binding inhibition of α-chymotrypsin by pNiXa is unaffected by Ni(II). Ovochymase in egg exudates is inhibited by pNiXa, but to a limited extent, even at high pNiXa concentrations. An octadecapeptide that models the His-rich domain (-HRHRHEQQGHHDSAKHGH-) of pNiXa forms six-coordinate, octahedral Ni(II)-complexes when the N-terminus is acetylated, and a square-planar Ni(II)-complex when the N-terminus is unblocked. Spectroscopy reveals two distinct types of octahedral Ni(II)-coordination to the N-acetylated octadecapeptide, involving, respectively, 3–4 and 5–6 imidazole nitrogens; the octadecapeptide undergoes partial, reversible precipitation in pH-and Ni(II)-dependent fashion, suggesting an insoluble, Ni(II)-coupled (Hx)n-dimer. Such (Hx)n-peptide interaction is confirmed by an enzyme-linked biotin-avidin assay with N-biotin-KHRHRHE-amide and N-acetyl-KHRHRHE-resin beads, which become coupled after adding Ni(II) or Zn(II). H2O2 oxidation of 2′-deoxyguanosine to mutagenic 8-hydroxy-2′deoxyguanosine is enhanced by the octahedral Ni(II)-octadecapeptide complex, although the effect is more intense with the square-planar Ni(II) octadecapeptide complex. Immunoperoxidase staining of whole mounts wish pNiXa antibody shows that pNiXa is distributed throughout gastrula-stage embryos and is localized during organogenesis in the brain, eye, spinal cord, myotomes, craniofacial tissues, and other sites of Ni(II) induced anomalies. Patterns of pNiXa staining are similar in controls and Ni(II)-exposed embryos. Binding of Ni(II) to pNiXa may cause embryotoxicity by enhancing oxidative reactions that produce tissue injury and genotoxicity. Although the natural target proteinases for pNiXa inhibition have not been established, pNiXa may be an important regulator of proteolysis during embryonic development. © 1996 Wiley-Liss, Inc. 相似文献
87.
88.
Pavel Bobrovsky Valentin Manuvera Izolda Baskova Svetlana Nemirova Alexandr Medvedev Vassili Lazarev 《Current issues in molecular biology》2021,43(3):2068
Leeches are amazing animals that can be classified as conditionally poisonous animals since the salivary cocktail they produce is injected directly into the victim, and its components have strictly defined biological purposes, such as preventing blood clot formation. Thrombolytic drugs are mainly aimed at treating newly formed blood clots. Aged clots are stabilized by a large number of isopeptide bonds that prevent the action of thrombolytics. These bonds are destroyed by destabilase, an enzyme of the leech’s salivary glands. Here, we conducted a pilot study to evaluate the feasibility and effectiveness of the use of destabilase in relation to blood clots formed during real pathological processes. We evaluated the isopeptidase activity of destabilase during the formation of a stabilized fibrin clot. We showed that destabilase does not affect the internal and external coagulation cascades. We calculated the dose–response curve and tested the ability of destabilase to destroy isopeptide bonds in natural blood clots. The effect of aged and fresh clots dissolving ability after treatment with destabilase coincided with the morphological characteristics of clots during surgery. Thus, recombinant destabilase can be considered as a potential drug for the treatment of aged clots, which are difficult to treat with known thrombolytics. 相似文献
89.
Svetlana Maslakova Christina I. Ellison Terra C. Hiebert Frances Conable Maureen C. Heaphy Dagoberto E. Venera-Pontn Jon L. Norenburg Megan L. Schwartz Nicole D. Moss Michael J. Boyle Amy C. Driskell Kenneth S. Macdonald III Eduardo E. Zattara Rachel Collin 《Biology letters》2022,18(4)
Biodiversity assessments are critical for setting conservation priorities, understanding ecosystem function and establishing a baseline to monitor change. Surveys of marine biodiversity that rely almost entirely on sampling adult organisms underestimate diversity because they tend to be limited to habitat types and individuals that can be easily surveyed. Many marine animals have planktonic larvae that can be sampled from the water column at shallow depths. This life stage often is overlooked in surveys but can be used to relatively rapidly document diversity, especially for the many species that are rare or live cryptically as adults. Using DNA barcode data from samples of nemertean worms collected in three biogeographical regions—Northeastern Pacific, the Caribbean Sea and Eastern Tropical Pacific—we found that most species were collected as either benthic adults or planktonic larvae but seldom in both stages. Randomization tests show that this deficit of operational taxonomic units collected as both adults and larvae is extremely unlikely if larvae and adults were drawn from the same pool of species. This effect persists even in well-studied faunas. These results suggest that sampling planktonic larvae offers access to a different subset of species and thus significantly increases estimates of biodiversity compared to sampling adults alone. Spanish abstract is available in the electronic supplementary material. 相似文献
90.
Sud'ina GF Pushkareva MA Galkina SI Surkov SA Mehl M Ullrich V 《Bioscience reports》1999,19(6):547-558
Human polymorphonuclear leukocytes (PMN) were found to tightly adhere on endothelial (lines EAhy926 and ECV304) and collagen surfaces under the influence of the chemotherapeutic drug suramin. This was observed by scanning electron microscopy and quantitated by myeloperoxidase assays. Suramin also inhibited Ca2+ ionophore A23187-stimulated leukotriene (LT) synthesis in PMN interaction with endothelial cells or with collagen surface. Suramin decreased the release of radiolabeled arachidonic acid (AA) and 5-lip-oxygenase (5-LO) metabolites by prelabeled PMN stimulated with A23187. Using agents releasing the suramin-stimulated adhesion namely jasplakonolide and dextran sulfate, we observed a reversal of the suramin effect on leukotriene synthesis. Jasplakonolide released the adhesion of PMN on endothelial and collagen-coated surfaces and restored 5-LO activity. Dextran-sulfate released adhesion on collagen-coated surfaces and abolished suramin inhibition. Arachidonate could also overcome adhesion and inhibition of 5-LO. We conclude that suramin-induced tight attachment of PMN on to solid surfaces lead to decreased leukotriene synthesis during subsequent A23187 stimulation in the absence of exogenous substrates. 相似文献