全文获取类型
收费全文 | 1789篇 |
免费 | 112篇 |
国内免费 | 2篇 |
专业分类
1903篇 |
出版年
2024年 | 4篇 |
2023年 | 20篇 |
2022年 | 31篇 |
2021年 | 61篇 |
2020年 | 33篇 |
2019年 | 47篇 |
2018年 | 35篇 |
2017年 | 30篇 |
2016年 | 67篇 |
2015年 | 96篇 |
2014年 | 115篇 |
2013年 | 108篇 |
2012年 | 161篇 |
2011年 | 120篇 |
2010年 | 80篇 |
2009年 | 72篇 |
2008年 | 109篇 |
2007年 | 111篇 |
2006年 | 76篇 |
2005年 | 82篇 |
2004年 | 87篇 |
2003年 | 63篇 |
2002年 | 74篇 |
2001年 | 9篇 |
2000年 | 9篇 |
1999年 | 15篇 |
1998年 | 18篇 |
1997年 | 13篇 |
1996年 | 13篇 |
1995年 | 7篇 |
1994年 | 11篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 11篇 |
1985年 | 7篇 |
1984年 | 13篇 |
1983年 | 4篇 |
1982年 | 12篇 |
1981年 | 3篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1977年 | 4篇 |
1969年 | 3篇 |
1968年 | 2篇 |
1957年 | 2篇 |
排序方式: 共有1903条查询结果,搜索用时 15 毫秒
961.
S?ren Johst Stephan Orzada Anja Fischer Lena C. Sch?fer Kai Nassenstein Lale Umutlu Thomas C. Lauenstein Mark E. Ladd Stefan Maderwald 《PloS one》2014,9(1)
In this study three sequences for non-contrast-enhanced MRA of the lower extremity arteries at 7T were compared. Cardiac triggering was used with the aim to reduce signal variations in the arteries. Two fast single-shot 2D sequences, a modified Ultrafast Spoiled Gradient Echo (UGRE) sequence and a variant of the Quiescent-Interval Single-Shot (QISS) sequence were triggered via phonocardiogram and compared in volunteer examinations to a non-triggered 2D gradient echo (GRE) sequence. For image acquisition, a 16-channel transmit/receive coil and a manually positionable AngioSURF table were used. To tackle B1 inhomogeneities at 7T, Time-Interleaved Acquisition of Modes (TIAMO) was integrated in GRE and UGRE. To compare the three sequences quantitatively, a vessel-to-background ratio (VBR) was measured in all volunteers and stations. In conclusion, cardiac triggering was able to suppress flow artifacts satisfactorily. The modified UGRE showed only moderate image artifacts. Averaged over all volunteers and stations, GRE reached a VBR of 4.18±0.05, UGRE 5.20±0.06, and QISS 2.72±0.03. Using cardiac triggering and TIAMO imaging technique was essential to perform non-enhanced MRA of the lower extremities vessels at 7T. The modified UGRE performed best, as observed artifacts were only moderate and the highest average VBR was reached. 相似文献
962.
Malin Wennstr?m Shorena Janelidze Cecilie Bay-Richter Lennart Minthon Lena Brundin 《PloS one》2014,9(10)
Neuron glial 2 (NG2) cells become strongly activated in injured brain areas. The activation is characterized by increased proliferation as well as increased expression and shedding of the proteoglycan NG2 expressed on their cell surface. It is currently not known how these cells respond to low-grade neuroinflammation provoked by systemic inflammation. To investigate this, we analyzed NG2 cell proliferation as well as soluble NG2 (sNG2) in cerebrospinal fluid (CSF) from rats treated with an acute intraperitoneal (i.p) injection of lipopolysaccharides (LPS) or saline and sacrificed after 2 or 24 hours. The systemically induced neuroinflammation was confirmed as elevated levels of cytokines, including interleukin (IL)-6 and IL-1β, and MHCII expressing microglia were found 24 h after LPS treatment. At this time point NG2 cell proliferation was significantly decreased in both amygdala and hippocampus and sNG2 levels in CSF were increased twofold. We also exposed human NG2 cells in culture to IL-6 and IL-1β for 24 h and found, in line with our in vivo study, a direct impact of these cytokines reducing cell proliferation and increasing shedding of NG2. We conclude that LPS induced systemic inflammation significantly affects NG2 cell proliferation and shedding and that these two events at least in in part are mediated by IL-6 and IL-1β. 相似文献
963.
Michael Ingre Göran Kecklund Torbjörn Åkerstedt Marie Söderström Lena Kecklund 《Chronobiology international》2013,30(2-3):349-358
Forty‐six male train drivers (mean age=46.5, SD=5.1) were recruited to participate in a diary study for 14 consecutive days with questions about their sleep and working hours. A polynomial mixed‐effect regression model showed a curvilinear relation (p <. 001) between shift‐start time and sleep duration for shifts starting at 03∶00–12∶00 h and with a near linear increase for ones starting between 04∶30 and 09∶00 h of approximately 0.7 h for every 1 h the shift was delayed. The longest sleeps were estimated at ~8 h before shifts that started at ~10∶00 h. The shortest sleeps were found for shifts that started before 04∶30 h and were estimated at ~5 h. Individual differences were estimated with a random-effect standard deviation of 0.51 h, independent of shift‐start time (p =.005). One‐half of the between‐subject variance was explained by subjective health. A one‐step decrease in health was associated with a 26 min increase in sleep length. The results have practical implications for constructing shift schedules. Early morning shifts reduced sleep length substantially and should be mixed with later start hours to avoid the accumulation of sleep dept. Delaying the shift‐start past 10∶00 h had little effect on sleep opportunity; however, delaying shift‐start to between 04∶30 and 9∶00 h had a strong impact on sleep length, with 70% of the extra time used for sleep, suggesting large positive effects for this range of shift‐start times. 相似文献
964.
Typically, pathogens infect multiple host species. Such multihost pathogens can show considerable variation in their degree of infection and transmission specificity, which has important implications for potential disease emergence. Transmission of multihost pathogens can be driven by key host species and changes in such transmission networks can lead to disease emergence. We study two viruses that show contrasting patterns of prevalence and specificity in managed honeybees and wild bumblebees, black queen cell virus (BQCV) and slow bee paralysis virus (SBPV), in the context of the novel transmission route provided by the virus‐vectoring Varroa destructor. Our key result is that viral communities and RNA virus genetic variation are structured by location, not host species or V. destructor presence. Interspecific transmission is pervasive with the same viral variants circulating between pollinator hosts in each location; yet, we found virus‐specific host differences in prevalence and viral load. Importantly, V. destructor presence increases the prevalence in honeybees and, indirectly, in wild bumblebees, but in contrast to its impact on deformed wing virus (DWV), BQCV and SBPV viral loads are not increased by Varroa presence, and do not show genetic evidence of recent emergence. Effective control of Varroa in managed honeybee colonies is necessary to mitigate further disease emergence, and alleviate disease pressure on our vital wild bee populations. More generally, our results highlight the over‐riding importance of geographical location to the epidemiological outcome despite the complexity of multihost‐parasite interactions. 相似文献
965.
966.
Lundin L Rönnstrand L Cross M Hellberg C Lindahl U Claesson-Welsh L 《Experimental cell research》2003,287(1):190-198
The sulfated regions in heparan sulfate and heparin are known to affect fibroblast growth factor (FGF) function. We have studied the mechanism whereby heparin directs FGF-2-induced FGF receptor-1 (FGFR-1) signal transduction. FGF-2 alone stimulated maximal phosphorylation of Src homology domain 2 tyrosine phosphatase (SHP-2) and the adaptor molecule Crk, in heparan sulfate-deficient Chinese hamster ovary (CHO) 677 cells expressing FGFR-1. In contrast, for phospholipase Cgamma(1) (PLCgamma(1)) and the adaptor molecule Shb to be maximally tyrosine-phosphorylated, cells had to be stimulated with both FGF-2 and heparin (100 ng/ml). Tyrosine residues 463 in the juxtamembrane domain and 766 in the C-terminal tail in FGFR-1 are known to bind Crk and PLCgamma(1), respectively. Analysis of tryptic phosphopeptide maps of FGFR-1 from cells stimulated with FGF-2 alone and FGF-2 together with heparin showed that FGF-2 alone stimulated a several-fold increase in tyrosine 463 in the juxtamembrane domain. In contrast, heparin had to be included in order for tyrosine 766 to be phosphorylated to the same fold level. Our data imply that tyrosine 463 is phosphorylated and able to transduce signals in response to FGF-2 treatment alone; furthermore, we suggest that FGFR-1 dimerization/kinase activation is stabilized by heparin. 相似文献
967.
Jill C. Preston Lena C. Hileman 《The Plant journal : for cell and molecular biology》2010,62(4):704-712
The degree to which developmental genetic pathways are conserved across distantly related organisms is a major question in biology. In Arabidopsis thaliana (L.) Heynh., inflorescence development is initiated in response to a combination of external and internal floral inductive signals that are perceived across the whole plant, but are integrated within the shoot apical meristem. Recently, it was demonstrated that SQUAMOSA‐PROMOTER BINDING PROTEIN (SBP)‐box proteins regulate A. thaliana flowering time by mediating signals from the autonomous and photoperiod pathways, and by directly activating key genes involved in inflorescence and floral meristem identity, including FRUITFULL (FUL), APETALA1 (AP1) and LEAFY (LFY). In the distantly related core eudicot species Antirrhinum majus L., paralogous SBP‐box proteins SBP1 and SBP2 have likewise been implicated in regulating the AP1 ortholog SQUAMOSA (SQUA). To test the hypothesis that SBP‐box genes are also involved in the floral induction of A. majus, we used a reverse genetic approach to silence SBP1. SBP1‐silenced lines are late to nonflowering, and show reduced apical dominance. Furthermore, expression and sequence analyses suggest that the SBP1‐mediated transition to flowering occurs through the positive regulation of FUL/LFY homologs. Together, these data outline the utility of virus‐induced gene silencing in A. majus, and provide new insight into the conservation of flowering time genetic pathways across core eudicots. 相似文献
968.
Sawada K Hasegawa M Tokuda L Kameyama J Kodama O Kohchi T Yoshida K Shinmyo A 《Bioscience, biotechnology, and biochemistry》2004,68(4):873-880
The rice Oryza sativa selenium-binding protein homologue (OsSBP) gene encodes a homologue of mammalian selenium-binding proteins, and it has been isolated as one of the genes induced by treating a plant with a cerebroside elicitor from rice blast fungus. The possible role of OsSBP in plant defense was evaluated by using a transgenic approach. Plants overexpressing OsSBP showed enhanced resistance to a virulent strain of rice blast fungus as well as to rice bacterial blight. The expression of defense-related genes and the accumulation of phytoalexin after infection by rice blast fungus were accelerated in the OsSBP overexpressors. A higher level of H(2)O(2) accumulation and reduced activity of such scavenging enzymes as ascorbate peroxidase and catalase were seen when the OsSBP-overexpressing plants were treated with the protein phosphatase 1 inhibitor, calyculin A. These results suggest that the upregulation of OsSBP expression conferred enhanced tolerance to different pathogens, possibly by increasing plant sensitivity to endogenous defense responses. Additionally, the OsSBP protein might have a role in modulating the defense mechanism to biotic stress in rice. 相似文献
969.
Asa Wilsson Sara Lind Lena Ohman Asa Nilsdotter-Augustinsson Helen Lundqvist-Setterud 《FEMS immunology and medical microbiology》2008,53(1):126-135
Staphylococcus epidermidis infections are usually nosocomial and involve colonization of biomaterials. The immune defense system cannot efficiently control the bacteria during these infections, which often results in protracted chronic inflammation, in which a key event is disturbed removal of neutrophils by tissue macrophages. While ingesting uninfected apoptotic neutrophils, macrophages release anti-inflammatory cytokines that lead to resolution of inflammation. In clinical studies, we have previously found elevated levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 in synovial fluid from prostheses infected with coagulase negative staphylococci. We show that macrophages phagocytosing apoptotic neutrophils containing S. epidermidis released TNF-alpha and interleukin-6, whereas macrophages phagocytosing spontaneously apoptotic neutrophils did not. This difference was not due to dissimilar phagocytic capacities, because macrophages ingested both types of neutrophils to the same extent. The activation was induced mainly by the apoptotic neutrophils themselves, not by the few remaining extracellular bacteria. Macrophages were not activated by apoptotic neutrophils that contained paraformaldehyde-killed S. epidermidis. Proinflammatory reactions induced by clearance of apoptotic neutrophils containing S. epidermidis might represent an important mechanism to combat the infective agent. This activation of macrophages may contribute to the development of chronic inflammation instead of inflammation resolution. 相似文献
970.
A systems biology approach reveals major metabolic changes in the thermoacidophilic archaeon Sulfolobus solfataricus in response to the carbon source L‐fucose versus D‐glucose 下载免费PDF全文
Jacqueline Wolf Helge Stark Katharina Fafenrot Andreas Albersmeier Trong K. Pham Katrin B. Müller Benjamin H. Meyer Lena Hoffmann Lu Shen Stefan P. Albaum Theresa Kouril Kerstin Schmidt‐Hohagen Meina Neumann‐Schaal Christopher Bräsen Jörn Kalinowski Phillip C. Wright Sonja‐Verena Albers Dietmar Schomburg Bettina Siebers 《Molecular microbiology》2016,102(5):882-908
Archaea are characterised by a complex metabolism with many unique enzymes that differ from their bacterial and eukaryotic counterparts. The thermoacidophilic archaeon Sulfolobus solfataricus is known for its metabolic versatility and is able to utilize a great variety of different carbon sources. However, the underlying degradation pathways and their regulation are often unknown. In this work, the growth on different carbon sources was analysed, using an integrated systems biology approach. The comparison of growth on L‐fucose and D‐glucose allows first insights into the genome‐wide changes in response to the two carbon sources and revealed a new pathway for L‐fucose degradation in S. solfataricus. During growth on L‐fucose major changes in the central carbon metabolic network, as well as an increased activity of the glyoxylate bypass and the 3‐hydroxypropionate/4‐hydroxybutyrate cycle were observed. Within the newly discovered pathway for L‐fucose degradation the following key reactions were identified: (i) L‐fucose oxidation to L‐fuconate via a dehydrogenase, (ii) dehydration to 2‐keto‐3‐deoxy‐L‐fuconate via dehydratase, (iii) 2‐keto‐3‐deoxy‐L‐fuconate cleavage to pyruvate and L‐lactaldehyde via aldolase and (iv) L‐lactaldehyde conversion to L‐lactate via aldehyde dehydrogenase. This pathway as well as L‐fucose transport shows interesting overlaps to the D‐arabinose pathway, representing another example for pathway promiscuity in Sulfolobus species. 相似文献