全文获取类型
收费全文 | 1612篇 |
免费 | 128篇 |
国内免费 | 1篇 |
专业分类
1741篇 |
出版年
2023年 | 6篇 |
2022年 | 10篇 |
2021年 | 33篇 |
2020年 | 20篇 |
2019年 | 27篇 |
2018年 | 20篇 |
2017年 | 26篇 |
2016年 | 42篇 |
2015年 | 68篇 |
2014年 | 55篇 |
2013年 | 120篇 |
2012年 | 118篇 |
2011年 | 127篇 |
2010年 | 99篇 |
2009年 | 90篇 |
2008年 | 123篇 |
2007年 | 90篇 |
2006年 | 87篇 |
2005年 | 93篇 |
2004年 | 99篇 |
2003年 | 96篇 |
2002年 | 101篇 |
2001年 | 18篇 |
2000年 | 15篇 |
1999年 | 21篇 |
1998年 | 17篇 |
1997年 | 12篇 |
1996年 | 15篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 10篇 |
1992年 | 14篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 11篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有1741条查询结果,搜索用时 0 毫秒
51.
Background
Worldwide, finfish fisheries are receiving increasing assessment and regulation, slowly leading to more sustainable exploitation and rebuilding. In their wake, invertebrate fisheries are rapidly expanding with little scientific scrutiny despite increasing socio-economic importance.Methods and Findings
We provide the first global evaluation of the trends, drivers, and population and ecosystem consequences of invertebrate fisheries based on a global catch database in combination with taxa-specific reviews. We also develop new methodologies to quantify temporal and spatial trends in resource status and fishery development. Since 1950, global invertebrate catches have increased 6-fold with 1.5 times more countries fishing and double the taxa reported. By 2004, 34% of invertebrate fisheries were over-exploited, collapsed, or closed. New fisheries have developed increasingly rapidly, with a decrease of 6 years (3 years) in time to peak from the 1950s to 1990s. Moreover, some fisheries have expanded further and further away from their driving market, encompassing a global fishery by the 1990s. 71% of taxa (53% of catches) are harvested with habitat-destructive gear, and many provide important ecosystem functions including habitat, filtration, and grazing.Conclusions
Our findings suggest that invertebrate species, which form an important component of the basis of marine food webs, are increasingly exploited with limited stock and ecosystem-impact assessments, and enhanced management attention is needed to avoid negative consequences for ocean ecosystems and human well-being. 相似文献52.
The WD repeat protein FAN regulates lysosome size independent from abnormal downregulation/membrane recruitment of protein kinase C 总被引:1,自引:0,他引:1
Möhlig H Mathieu S Thon L Frederiksen MC Ward DM Kaplan J Schütze S Kabelitz D Adam D 《Experimental cell research》2007,313(12):2703-2718
FAN (factor associated with neutral sphingomyelinase [N-SMase] activation) exhibits striking structural homologies to Lyst (lysosomal trafficking regulator), a BEACH protein whose inactivation causes formation of giant lysosomes/Chediak-Higashi syndrome. Here, we show that cells lacking FAN show a statistically significant increase in lysosome size (although less pronounced as Lyst), pointing to previously unrecognized functions of FAN in regulation of the lysosomal compartment. Since FAN regulates activation of N-SMase in complex with receptor for activated C-kinase (RACK)1, a scaffolding protein that recruits and stabilizes activated protein kinase C (PKC) isotypes at cellular membranes, and since an abnormal (calpain-mediated) downregulation/membrane recruitment of PKC has been linked to the defects observed in Lyst-deficient cells, we assessed whether PKC is also of relevance in FAN signaling. Our results demonstrate that activation of PKC is not required for regulation of N-SMase by FAN/RACK1. Conversely, activation of PKC and recruitment/stabilization by RACK1 occurs uniformly in the presence or absence of FAN (and equally, Lyst). Furthermore, regulation of lysosome size by FAN is not coupled to an abnormal downregulation/membrane recruitment of PKC by calpain. Identical results were obtained for Lyst, questioning the previously reported relevance of PKC for formation of giant lysosomes and in Chediak-Higashi syndrome. In summary, FAN mediates activation of N-SMase as well as regulation of lysosome size by signaling pathways that operate independent from activation/membrane recruitment of PKC. 相似文献
53.
Interactions of donor sources and media influence the histo‐morphological quality of full‐thickness skin models 下载免费PDF全文
Julia Lange Frederik Weil Christoph Riegler Florian Groeber Silke Rebhan Szymon Kurdyn Miriam Alb Hermann Kneitz Götz Gelbrich Heike Walles Stephan Mielke 《Biotechnology journal》2016,11(10):1352-1361
Human artificial skin models are increasingly employed as non‐animal test platforms for research and medical purposes. However, the overall histopathological quality of such models may vary significantly. Therefore, the effects of manufacturing protocols and donor sources on the quality of skin models built‐up from fibroblasts and keratinocytes derived from juvenile foreskins is studied. Histo‐morphological parameters such as epidermal thickness, number of epidermal cell layers, dermal thickness, dermo‐epidermal adhesion and absence of cellular nuclei in the corneal layer are obtained and scored accordingly. In total, 144 full‐thickness skin models derived from 16 different donors, built‐up in triplicates using three different culture conditions were successfully generated. In univariate analysis both media and donor age affected the quality of skin models significantly. Both parameters remained statistically significant in multivariate analyses. Performing general linear model analyses we could show that individual medium‐donor‐interactions influence the quality. These observations suggest that the optimal choice of media may differ from donor to donor and coincides with findings where significant inter‐individual variations of growth rates in keratinocytes and fibroblasts have been described. Thus, the consideration of individual medium‐donor‐interactions may improve the overall quality of human organ models thereby forming a reproducible test platform for sophisticated clinical research. 相似文献
54.
Heike K. Lotze Karsten Reise Boris Worm Justus van Beusekom Mette Busch Anneli Ehlers Dirk Heinrich Richard C. Hoffmann Poul Holm Charlotte Jensen Otto S. Knottnerus Nicole Langhanki Wietske Prummel Manfred Vollmer Wim J. Wolff 《Helgoland Marine Research》2005,59(1):84-95
Todays Wadden Sea is a heavily human-altered ecosystem. Shaped by natural forces since its origin 7,500 years ago, humans gradually gained dominance in influencing ecosystem structure and functioning. Here, we reconstruct the timeline of human impacts and the history of ecological changes in the Wadden Sea. We then discuss the ecosystem and societal consequences of observed changes, and conclude with management implications. Human influences have intensified and multiplied over time. Large-scale habitat transformation over the last 1,000 years has eliminated diverse terrestrial, freshwater, brackish and marine habitats. Intensive exploitation of everything from oysters to whales has depleted most large predators and habitat-building species since medieval times. In the twentieth century, pollution, eutrophication, species invasions and, presumably, climate change have had marked impacts on the Wadden Sea flora and fauna. Yet habitat loss and overexploitation were the two main causes for the extinction or severe depletion of 144 species (~20% of total macrobiota). The loss of biodiversity, large predators, special habitats, filter and storage capacity, and degradation in water quality have led to a simplification and homogenisation of the food web structure and ecosystem functioning that has affected the Wadden Sea ecosystem and coastal societies alike. Recent conservation efforts have reversed some negative trends by enabling some birds and mammals to recover and by creating new economic options for society. The Wadden Sea history provides a unique long-term perspective on ecological change, new objectives for conservation, restoration and management, and an ecological baseline that allows us to envision a rich, productive and diverse Wadden Sea ecosystem and coastal society. 相似文献
55.
Subcellular volumes and metabolite concentrations in barley leaves 总被引:25,自引:1,他引:25
Metabolite concentrations in subcellular compartments from mature barley (Hordeum vulgare L. cv. Apex) leaves after 9 h of illumination and 5 h of darkness were determined by nonaqueous fractionation and by the stereological evaluation of cellular and subcellular volumes from light and electron micrographs. Twenty one-day-old primary leaves of barley with a total leaf volume of 902 μL per mg chlorophyll were found to be composed of 27% epidermis, 42% mesophyll cells, 6% veins, 4.5% apoplast and 23% gas space. While in epidermal cells 99% of the volume was occupied by the vacuole, mesophyll cells with an average volume of 31.3 pL consisted of 23 pL (73%) vacuole, 4.6 pL (19%) chloroplasts, 2.06 pL (6,7%) cytosol (including smaller organelles and vesicles), 0.34 pL (1%) mitochondria and 107 fL (0.34%) nucleus. The differences between leaves harvested after 9 h of illumination and after 5 h of darkness were in the size of the stromal compartment and the starch grains therein. Subcellular metabolite concentrations were calculated from the compartmental volumes and metabolite contents of the compartments as determined by nonaqueous fractionation. The amino-acid concentrations in stroma and cytosol were rather similar after 9 h of illumination and 5 h of darkness. In contrast, the vacuolar amino-acid concentrations were about one order of magnitude lower than the stroma and cytosol values, and there was a slight increase in concentration after 5 h of darkness. 相似文献
56.
Prof. Dr. Wolf-Christian Dullo Dr. Marcos Gektidis Prof. Dr. Stjepko Golubic Dr. Georg A. Heiss Dipl. Biol. Heike Kampmann Dr. William Kiene Dipl. Ökol. Dieter K. Kroll Dipl. Biol. Martin L. Kuhrau Dr. Gudrun Radtke Dr. John G. Reijmer Dr. Götz B. Reinicke Prof. Dr. Dietrich Schlichter Prof. Dr. Helmut Schuhmacher Klaus Vogel 《Facies》1995,32(1):145-188
57.
The turn-inducing sequence Ala-Aib introduced into positions 31 and 32 of neuropeptide Y (NPY) and its analogues has been identified as the key structure for Y(5)-receptor selectivity. Analogues of NPY and PP/NPY chimera containing the motif Ala-Aib were prepared; these peptides turned out to be selective for the Y(5)-receptor. The affinity of the NPY-based peptides was in the range of 6-150 nM, while the affinity of three (Ala-Aib)-containing PP/NPY chimera was in the range of 0.2-0.9 nM. The circular dichroism spectra of the Aib analogues in aqueous solution were all characteristic of an alpha helix; however, they had different intensities of the two negative bands at 220 and 208 nm. Affinity and selectivity for the Y(5)-receptor were correlated with the ratio of the ellipticity at 220 nm versus the one at 208 nm (R), which indicates the presence of a pronounced helix (R > 1) versus a less stabile one (R < 1). When R was in the range 0.74-0.96, the affinity at the Y(5)-receptor was in the range >5 nM, while there was complete loss of affinity at the Y(4)-receptor. R > 1.15 was associated with very high affinity at the Y(5)-receptor and weak affinity at the Y(4)-receptor. These results suggest that the selectivity of the Ala(31)-Aib(32) motif for the Y(5)-receptor derives from a specific conformation that must be correlated with the bioactive conformation of NPY at this subtype. 相似文献
58.
Linzhu Gou Simone Robl Kai Leonhard Heike Lorenz Magdalena Sordo Annamaria Butka Stefan Kesselheim Morris Wolff Andreas Seidel‐Morgenstern Karlheinz Schaber 《Chirality》2011,23(2):118-127
The resolution of chiral compound‐forming systems using hybrid processes was discussed recently. The concept is of large relevance as these systems form the majority of chiral substances. In this study, a novel hybrid process is presented, which combines pertraction and subsequent preferential crystallization and is applicable for the resolution of such systems. A supported liquid membrane applied in a pertraction process provides enantiomeric enrichment. This membrane contains a solution of a chiral compound acting as a selective carrier for one of the enantiomers. Screening of a large number of liquid membranes and potential carriers using the conductor‐like screening model for realistic solvation method led to the identification of several promising carriers, which were tested experimentally in several pertraction runs aiming to yield enriched (+)‐(S)‐mandelic acid (MA) solutions from racemic feed solutions. The most promising system consisted of tetrahydronaphthalene as liquid membrane and hydroquinine‐4‐methyl‐2‐quinolylether (HMQ) as chiral carrier achieving enantiomeric excesses of 15% in average. The successful production of (+)‐(S)‐MA with a purity above 96% from enriched solutions by subsequent preferential crystallization proved the applicability of the hybrid process. Chirality, 2011. © 2010 Wiley‐Liss, Inc. 相似文献
59.
Heike Schmidt Rüdiger Bode Ida A. Samsonova Dieter Birnbaum 《Applied microbiology and biotechnology》1989,31(5-6):463-466
Summary Mutants of Candida maltosa were isolated that lacked saccharopine reductase (lys9) and saccharopine dehydrogenase (lys1) and were able to accumulate -aminoadipate--semialdehyde (AASA) in the cell and excrete it into the culture medium. The effects of incubation time, lysine concentration, and carbon and nitrogen sources on AASA production were examined. In the presence of 15 g glucose/1, 1.25 g NH4H2PO4/l and 50 mg l-lysine/l in a minimal salt medium C. maltosa G285 (lys1) produced about 80–90 mg AASA/l during 48 h of growth. A simple and rapid procedure to isolate AASA from the medium using Dowex 50X4 is described. 相似文献
60.
Hagen Körschgen Marius Baeken Daniel Schmitt Heike Nagel Christian Behl 《Traffic (Copenhagen, Denmark)》2023,24(12):564-575
The co-chaperone BAG3 is a hub for a variety of cellular pathways via its multiple domains and its interaction with chaperones of the HSP70 family or small HSPs. During aging and under cellular stress conditions in particular, BAG3, together with molecular chaperones, ensures the sequestration of aggregated or aggregation-prone ubiquitinated proteins to the autophagic-lysosomal system via ubiquitin receptors. Accumulating evidence for BAG3-mediated selective autophagy independent of cargo ubiquitination led to analyses predicting a direct interaction of BAG3 with LC3 proteins. Phylogenetically, BAG3 comprises several highly conserved potential LIRs, LC3-interacting regions, which might allow for the direct targeting of BAG3 including its cargo to autophagosomes and drive their autophagic degradation. Based on pull-down experiments, peptide arrays and proximity ligation assays, our results provide evidence of an interaction of BAG3 with LC3B. In addition, we could demonstrate that disabling all predicted LIRs abolished the inducibility of a colocalization of BAG3 with LC3B-positive structures and resulted in a substantial decrease of BAG3 levels within purified native autophagic vesicles compared with wild-type BAG3. These results suggest an autophagic targeting of BAG3 via interaction with LC3B. Therefore, we conclude that, in addition to being a key co-chaperone to HSP70, BAG3 may also act as a cargo receptor for client proteins, which would significantly extend the role of BAG3 in selective macroautophagy and protein quality control. 相似文献