全文获取类型
收费全文 | 622篇 |
免费 | 34篇 |
出版年
2024年 | 1篇 |
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 8篇 |
2020年 | 7篇 |
2019年 | 11篇 |
2018年 | 13篇 |
2017年 | 7篇 |
2016年 | 13篇 |
2015年 | 24篇 |
2014年 | 23篇 |
2013年 | 22篇 |
2012年 | 45篇 |
2011年 | 32篇 |
2010年 | 26篇 |
2009年 | 29篇 |
2008年 | 36篇 |
2007年 | 30篇 |
2006年 | 26篇 |
2005年 | 34篇 |
2004年 | 35篇 |
2003年 | 28篇 |
2002年 | 24篇 |
2001年 | 9篇 |
2000年 | 16篇 |
1999年 | 12篇 |
1998年 | 9篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 7篇 |
1994年 | 3篇 |
1993年 | 10篇 |
1992年 | 12篇 |
1991年 | 13篇 |
1990年 | 9篇 |
1989年 | 8篇 |
1988年 | 7篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 9篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1977年 | 2篇 |
1975年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有656条查询结果,搜索用时 15 毫秒
101.
Phenotypic variation in a family with mutations in two Hirschsprung-related genes (RET and endothelin receptor B) 总被引:4,自引:0,他引:4
P.-J. Svensson Maria Anvret Marie-Louise Molander Agneta Nordenskjöld 《Human genetics》1998,103(2):145-148
Hirschsprung disease is a congenital malformation affecting 1 in 5000 live births. The absence of parasympathetic neuronal
ganglia (Meissner, Auerbach) in the hindgut results in poor coordination of peristaltic movement, and a varying degree of
constipation. Four different genes have been implicated in the pathogenesis of Hirschsprung disease: the RET tyrosine kinase
receptor gene; one of its ligands, the glial cell line-derived neurotrophic factor (GDNF) gene; the endothelin receptor B
(EDNRB) gene; and its ligand, endothelin-3 (EDN3). Recently, combinations of mutations in two of these genes (RET and GDNF)
have been reported in Hirschsprung patients. We report a family with missense mutations in both the RET gene (R982C) and the
EDNRB gene (G57S). In this family, three out of five members have the two mutations, but only one, a boy, has the Hirschsprung
disease phenotype. This illustrates the complexity of the molecular background of Hirschsprung disease.
Received: 23 January 1998 / Accepted: 24 March 1998 相似文献
102.
B Losman M Biller S Olofsson K Sch?nning O S Lund B Svennerholm J E Hansen A Bolmstedt 《FEBS letters》1999,454(1-2):47-52
We have previously shown that an N-glycosylation site of N306 of HIV-1 gp120 is not necessary for the HIV-1 infectivity but protects HIV-1 from neutralising antibodies. In contrast Nakayama et al. [FEBS Lett. (1998) 426, 367-372], using a virus with an identical V3 region, suggested that elimination of this particular glycan reduced the ability of T-tropic HIV to bind to CXCR4 and hence its ability to infect T cell lines. We therefore re-examined the ability of a mutant virus, lacking the N306 glycan, to replicate in various types of cells and found no change in co-receptor usage for mutant virus. The ability of mutant virus to replicate or to induce syncytia in infected cells was similar to that of wild type virus. These results corroborate our original observation, confirming that the induced mutation in the N306 glycosylation site neither impairs nor improves the ability of mutant virus to replicate in permissive cells. 相似文献
103.
Ileana Manduteanu Dan Simionescu Agneta Simionescu Maya Simionescu 《Journal of cellular and molecular medicine》2021,25(20):9483-9495
Valve disease and particularly calcific aortic valve disease (CAVD) and diabetes (DM) are progressive diseases constituting a global health burden for all aging societies (Progress in Cardiovascular Diseases. 2014;56(6):565: Circulation Research. 2021;128(9):1344). Compared to non-diabetic individuals (The Lancet. 2008;371(9626):1800: The American Journal of Cardiology. 1983;51(3):403: Journal of the American College of Cardiology. 2017;69(12):1523), the diabetic patients have a significantly greater propensity for cardiovascular disorders and faster degeneration of implanted bioprosthetic aortic valves. Previously, using an original experimental model, the diabetic-hyperlipemic hamsters, we have shown that the earliest alterations induced by these conditions occur at the level of the aortic valves and, with time these changes lead to calcifications and CAVD. However, there are no pharmacological treatments available to reverse or retard the progression of aortic valve disease in diabetes, despite the significant advances in the field. Therefore, it is critical to uncover the mechanisms of valve disease progression, find biomarkers for diagnosis and new targets for therapies. This review aims at presenting an update on the basic research in CAVD in the context of diabetes. We provide an insight into the accumulated data including our results on diabetes-induced progressive cell and molecular alterations in the aortic valve, new potential biomarkers to assess the evolution and therapy of the disease, advancement in targeted nanotherapies, tissue engineering and the potential use of circulating endothelial progenitor cells in CAVD. 相似文献
104.
Wiebke Sihver† Karl-Johan Fasth rew G. Horti† rei O. Koren† Mats Bergström Li Lu Gisela Hagberg Hans Lundqvist§ Robert F. Dannals† Edythe D. London† Agneta Nordberg & Bengt Långström 《Journal of neurochemistry》1999,73(3):1264-1272
5-[76Br]Bromo-3-[[2(S)-azetidinyl]methoxy]pyridine ([76Br]BAP), a novel nicotinic acetylcholine receptor ligand, was synthesized using [76Br]bromide in an oxidative bromodestannylation of the corresponding trimethylstannyl compound. The radiochemical yield was 25%, and the specific radioactivity was on the order of 1 Ci/micromol. The binding properties of [76Br]BAP were characterized in vitro and in vivo in rat brain, and positron emission tomography (PET) experiments were performed in two rhesus monkeys. In association experiments on membranes of the cortex and thalamus, >90% of maximal specific [76Br]BAP binding was obtained after 60 min. The dissociation half-life of [76Br]BAP was 51 +/- 6 min in cortical membranes and 56 +/- 3 min in thalamic membranes. Saturation experiments with [76Br]BAP revealed one population of binding sites with dissociation constant (K(D)) values of 36 +/- 9 and 30 +/- 9 pM in membranes of cortex and thalamus, respectively. The maximal binding site density (Bmax) values were 90 +/- 17 and 207 +/- 33 fmol/mg in membranes of cortex and thalamus, respectively. Scatchard plots were nonlinear, and the Hill coefficients were <1, suggesting the presence of a lower-affinity binding site. In vitro autoradiography studies showed that binding of [76Br]BAP was high in the thalamus and presubiculum, moderate in the cortex and striatum, and low in the cerebellum and hippocampus. A similar pattern of [76Br]BAP accumulation was observed by ex vivo autoradiography. In vivo, binding of [76Br]BAP in whole rat brain was blocked by preinjection of (S)(-)-nicotine (0.3 mg/kg) by 27, 52, 68, and 91% at survival times of 10, 25, 40, 120, and 300 min, respectively. In a preliminary PET study in rhesus monkeys, the highest [76Br]BAP uptake was found in the thalamus, and radioactivity was displaceable by approximately 60% with cytisine and by 50% with (S)(-)-nicotine. The data of this study indicate that [76Br]BAP is a promising radioligand for the characterization of nicotinic acetylcholine receptors in vivo. 相似文献
105.
Caroline Sharmilee Josefin Karlsson Sofiia Miliutenko Anna Björklund Ulla Mörtberg Bo Olofsson Susanna Toller 《The International Journal of Life Cycle Assessment》2017,22(8):1302-1317
Purpose
The purpose of the study was to outline and demonstrate a new geographic information system (GIS)-based approach for utilising spatial geological data in three dimensions (i.e. length, width and depth) to improve estimates on earthworks during early stages of road infrastructure planning.Methods
This was undertaken by using three main methodological steps: mass balance calculation, life cycle inventory analysis and spatial mapping of greenhouse gas (GHG) emissions and energy use. The mass balance calculation was undertaken in a GIS environment using two assumptions of geological stratigraphy for two proposed alternative road corridors in Sweden. The estimated volumes of excavated soil, blasted rock and filling material were later multiplied with the GHG emission and energy use factors for these processes, to create spatial data and maps in order to show potential impacts of the studied road corridors. The proposed GIS-based approach was evaluated by comparing with actual values received after one alternative was constructed.Results and discussion
The results showed that the estimate of filling material was the most accurate (about 9 % deviation from actual values), while the estimate for excavated soil and blasted rock resulted in about 38 and 80 % deviation, respectively, from the actual values. It was also found that the total volume of excavated and ripped soils did not change when accounting for stratigraphy.Conclusions
The conclusion of this study was that more information regarding embankment height and actual soil thickness would further improve the model, but the proposed GIS-based approach shows promising results for usage in LCA at an early stage of road infrastructure planning. Thus, by providing better data quality, GIS in combination with LCA can enable planning for a more sustainable transport infrastructure.106.
107.
Melican K Boekel J Månsson LE Sandoval RM Tanner GA Källskog O Palm F Molitoris BA Richter-Dahlfors A 《Cellular microbiology》2008,10(10):1987-1998
Ascending urinary tract infections can cause extensive damage to kidney structure and function. We have used a number of advanced techniques including multiphoton microscopy to investigate the crucial early phases of uropathogenic Escherichia coli induced pyelonephritis within a living animal. Our results reveal a previously undescribed innate vascular response to mucosal infection, allowing isolation and eradication of the pathogen. The extremely rapid host response to mucosal infection was highlighted by the triggering of a cascade of events within 3-4 h. Epithelial signalling produced an increase in cellular O(2) consumption and affected microvascular flow by clotting, causing localized ischaemia. Subsequent ischaemic damage affected pathophysiology with actin re-arrangement and epithelial sloughing leading to paracellular bacterial movement. A denuded tubular basement membrane is shown to hinder immediate dissemination of bacteria, giving the host time to isolate the infection by clotting. Suppression of clotting by heparin treatment caused fatal urosepsis. Clinically these findings may be relevant in antibiotics delivery in pyelonephritis patients and to the use of anticoagulants in sepsis. 相似文献
108.
At the end of embryogenesis, the ventral nerve cord (VNC) of Drosophila undergoes a shape change, termed condensation. During condensation the length of the VNC shortens by 25%, a process dependent on extracellular matrix deposited by hemocytes, an intact cytoskeleton of glia and neurons and neural activity. Here we show that cell death contributes to nerve cord shortening. Firstly, apoptosis occurs at the interface of the epidermis and the nerve cord where it plays a role in the separation of these two tissues. Separation precedes condensation and in conditions where separation is prevented, condensation fails. Secondly, many cells undergo apoptosis within VNC during condensation. This cell death is localized mainly to the posterior part of the nerve cord where more than half of all cell death occurs. Preventing apoptosis either in neurons or glia partially inhibits VNC shortening during condensation. Despite the importance of midline glia in axon tract development, preventing midline glia cell death results in normal hatching and adult formation. We find that undead midline glia are eliminated from the midline and become mispositioned or expelled from the nervous system. We suggest that this represent a form of pattern repair that operates to reduce the impact of the additional cells. 相似文献
109.
Johanna Thelaus Agneta Andersson Peter Mathisen Anna-Lena Forslund Laila Noppa & Mats Forsman 《FEMS microbiology ecology》2009,67(1):69-80
The natural reservoir of Francisella tularensis , the causative agent of tularaemia, is yet to be identified. We investigated the possibility that Francisella persists in natural aquatic ecosystems between outbreaks. It was hypothesized that nutrient-rich environments, with strong protozoan predation, favour the occurrence of the tularaemia bacterium. To investigate the differences in adaptation to aquatic environments of the species and subspecies of Francisella , we screened 23 strains for their ability to survive grazing by the ciliate Tetrahymena pyriformis . All the Francisella strains tested were consumed at a low rate, although significant differences between subspecies were found. The survival and virulence of gfp -labelled F. tularensis ssp. holarctica were then studied in a microcosm experiment using natural lake water, with varying food web complexities and nutrient availabilities. High nutrient conditions in combination with high abundances of nanoflagellates were found to favour F. tularensis ssp. holarctica . The bacterium was observed both free-living and within the cells of a nanoflagellate. Francisella tularensis entered a viable but nonculturable state during the microcosm experiment. When studied over a longer period of time, F. tularensis ssp. holarctica survived in the lake water, but loss of virulence was not prevented by either high nutrient availability or the presence of predators. 相似文献
110.
Robotics of human movements 总被引:1,自引:0,他引:1
Patrick van der Smagt Markus Grebenstein Holger Urbanek Nadine Fligge Michael Strohmayr Georg Stillfried Jonathon Parrish Agneta Gustus 《Journal of Physiology》2009,103(3-5):119
The construction of robotic systems that can move the way humans do, with respect to agility, stability and precision, is a necessary prerequisite for the successful integration of robotic systems in human environments. We explain human-centered views on robotics, based on the three basic ingredients (1) actuation; (2) sensing; and (3) control, and formulate detailed examples thereof. 相似文献