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   2023篇
  免费   183篇
  2021年   14篇
  2020年   14篇
  2019年   17篇
  2018年   37篇
  2017年   26篇
  2016年   30篇
  2015年   47篇
  2014年   55篇
  2013年   128篇
  2012年   89篇
  2011年   98篇
  2010年   47篇
  2009年   58篇
  2008年   82篇
  2007年   114篇
  2006年   109篇
  2005年   107篇
  2004年   111篇
  2003年   92篇
  2002年   75篇
  2001年   68篇
  2000年   76篇
  1999年   74篇
  1998年   31篇
  1997年   26篇
  1996年   27篇
  1995年   26篇
  1994年   19篇
  1993年   20篇
  1992年   38篇
  1991年   35篇
  1990年   44篇
  1989年   33篇
  1988年   28篇
  1987年   31篇
  1986年   27篇
  1985年   27篇
  1984年   18篇
  1983年   25篇
  1982年   16篇
  1981年   14篇
  1980年   17篇
  1979年   22篇
  1978年   13篇
  1977年   13篇
  1976年   8篇
  1974年   7篇
  1973年   14篇
  1972年   11篇
  1968年   9篇
排序方式: 共有2206条查询结果,搜索用时 15 毫秒
1.
2.
Recent studies on global climate change report that increase in seawater temperature leads to coastal ecosystem change, including coral bleaching in the tropic. In order to assess the effect of increased seawater temperature on a temperate coastal ecosystem, we studied the inter-annual variation in productivity of Laminaria japonica using long-term oceanographic observations for the Uwa Sea, southern Japan. The annual productivity estimates for L. japonica were 2.7 ± 2.5 (mean ± SD) kg wet wt. m−1 (length of rope) (2003/2004), 1.0 ± 0.6 kg wet wt. m−1 (2004/2005) and 12.1 ± 12.5 kg wet wt. m−1 (2005/2006). Our previous study using the same methodology at the same locality reported that the productivity was estimated for the 2001/2002 (33.3 ± 15.2 kg wet wt. m−1) and 2002/2003 (34.0 ± 8.7 kg wet wt. m−1) seasons. Productivity in 2003/2004 and 2004/2005 was significantly lower than in years 2001/2002, 2002/2003 and 2005/2006. A comparison of oceanographic conditions among the 5 years revealed the presence of threshold seawater temperature effects. When the average seawater temperature during the first 45 days of each experiment exceeded 15.5°C, productivity was reduced to about 10 % of that in cooler years. Moreover the analysis of growth and erosion rates indicates that when the seawater temperature was over 17.5°C, erosion rate exceeded growth rate. Thus, an increase of seawater temperature of just 1°C during winter drastically reduces the productivity of L. japonica in the Uwa Sea.  相似文献   
3.
4.
Major depressive disorder (MDD) is a common psychiatric disorder that involves marked disabilities in global functioning, anorexia, and severe medical comorbidities. MDD is associated with not only psychological and sociocultural problems, but also pervasive physical dysfunctions such as metabolic, neurobiological and immunological abnormalities. Nevertheless, the mechanisms underlying the interactions between these factors have yet to be determined in detail. The aim of the present study was to identify the molecular mechanisms responsible for the interactions between MDD and dysregulation of physiological homeostasis, including immunological function as well as lipid metabolism, coagulation, and hormonal activity in the brain. We generated depression-like behavior in mice using chronic mild stress (CMS) as a model of depression. We compared the gene expression profiles in the prefrontal cortex (PFC) of CMS and control mice using microarrays. We subsequently categorized genes using two web-based bioinformatics applications: Ingenuity Pathway Analysis and The Database for Annotation, Visualization, and Integrated Discovery. We then confirmed significant group-differences by analyzing mRNA and protein expression levels not only in the PFC, but also in the thalamus and hippocampus. These web tools revealed that hepatocyte nuclear factor 4 alpha (Hnf4a) may exert direct effects on various genes specifically associated with amine synthesis, such as genes involved in serotonin metabolism and related immunological functions. Moreover, these genes may influence lipid metabolism, coagulation, and hormonal activity. We also confirmed the significant effects of Hnf4a on both mRNA and protein expression levels in the brain. These results suggest that Hnf4a may have a critical influence on physiological homeostasis under depressive states, and may be associated with the mechanisms responsible for the interactions between MDD and the dysregulation of physiological homeostasis in humans.  相似文献   
5.
Recent studies have demonstrated that the energetic profitability (net energy intake potential; NEI potential) of a habitat, which is calculated as the gross energy gain from foraging minus the energy expenditure from swimming at a focal point, may be a useful tool for predicting the salmonid biomass. The effectiveness of the NEI potential should be tested in various systems. Even if the NEI potential is validated, its predictive accuracy and transferability could be limited if the cover habitat, which is known to be an important factor for determining salmonid abundance, is not considered. We tested whether the NEI potential is effective for predicting the salmonid biomass even in a stream with abundant cover and whether combining the NEI potential and cover effects can improve the predictability of fish biomass using a generalized linear model. Our results demonstrated that the NEI potential could generally predict the fish biomass (percent deviance explained?=?79.9 %), and the model that incorporated both the NEI potential and the cover ratio improved the predictive accuracy (percent deviance explained?=?88.5 %). These results suggest that energetic profitability can be an effective indicator for assessing habitat quality and is relatively transferable to other systems. Furthermore, when cover effects are considered, the habitat quality is more accurately represented; thus, combining the energetic profitability and the cover effects might improve the transferability of the assessment across habitats.  相似文献   
6.
Hypoxia is considered one of the microenvironmental factors associated with the malignant nature of glioblastoma. Thus, evaluating intratumoural distribution of hypoxia would be useful for therapeutic planning as well as assessment of its effectiveness during the therapy. Electron paramagnetic resonance imaging (EPRI) is an imaging technique which can generate quantitative maps of oxygen in vivo using the exogenous paramagnetic compound, triarylmethyl and monitoring its line broadening caused by oxygen. In this study, the feasibility of EPRI for assessment of oxygen distribution in the glioblastoma using orthotopic U87 and U251 xenograft model is examined. Heterogeneous distribution of pO2 between 0 and 50?mmHg was observed throughout the tumours except for the normal brain tissue. U251 glioblastoma was more likely to exhibit hypoxia than U87 for comparable tumour size (median pO2; 29.7 and 18.2?mmHg, p?=?.028, in U87 and U251, respectively). The area with pO2 under 10?mmHg on the EPR oximetry (HF10) showed a good correlation with pimonidazole staining among tumours with evaluated size. In subcutaneous xenograft model, irradiation was relatively less effective for U251 compared with U87. In conclusion, EPRI is a feasible method to evaluate oxygen distribution in the brain tumour.  相似文献   
7.
A tertiary structure prediction is described using Monte Carlo simulated annealing for the peptide fragment corresponding to residues 16-36 of bovine pancreatic trypsin inhibitor (BPTI). The simulation starts with randomly chosen initial conformations and is performed without imposing experimental constraints using energy functions given for generic interatomic interactions. Out of 20 simulation trials, seven conformations show a sheet-like structure--two strands connected by a turn--although this sheet-like structure is not as rigid as that observed in native BPTI. It is also shown that these conformations are mostly looped and exhibit a native-like right-handed twist. Unlike the case with the C-peptide of RNase A, no conspicuous alpha-helical structure is found in any of the final conformations obtained in the simulation. However, the lowest-energy conformation does not resemble exactly the native structure. This indicates that the rigid beta-sheet conformation of native BPTI merely corresponds to a local minimum of the energy function if the fragment with residues 16-36 is isolated from the native protein. A statistical analysis of all 20 final conformations suggests that the tendency for the peptide segments to form extended beta-strands is strong for those with residues 18-24, and moderate for those with residues 30-35. The segment of residues 25-29 does not tend to form any definite structure. In native BPTI, the former segments are involved in the beta-sheet and the latter in the turn. A folding scenario is also speculated from this analysis.  相似文献   
8.
The rate and association constants (kinetic constants) which comprise a seven state cross-bridge scheme were deduced by sinusoidal analysis in chemically skinned rabbit psoas muscle fibers at 20 degrees C, 200 mM ionic strength, and during maximal Ca2+ activation (pCa 4.54-4.82). The kinetic constants were then used to calculate the steady state probability of cross-bridges in each state as the function of MgATP, MgADP, and phosphate (Pi) concentrations. This calculation showed that 72% of available cross-bridges were (strongly) attached during our control activation (5 mM MgATP, 8 mM Pi), which agreed approximately with the stiffness ratio (active:rigor, 69 +/- 3%); active stiffness was measured during the control activation, and rigor stiffness after an induction of the rigor state. By assuming that isometric tension is a linear combination of probabilities of cross-bridges in each state, and by measuring tension as the function of MgATP, MgADP, and Pi concentrations, we deduced the force associated with each cross-bridge state. Data from the osmotic compression of muscle fibers by dextran T500 were used to deduce the force associated with one of the cross-bridge states. Our results show that force is highest in the AM*ADP.Pi state (A = actin, M = myosin). Since the state which leads into the AM*ADP.Pi state is the weakly attached AM.ADP.Pi state, we confirm that the force development occurs on Pi isomerization (AM.ADP.Pi --> AM*ADP.Pi). Our results also show that a minimal force change occurs with the release of Pi or MgADP, and that force declines gradually with ADP isomerization (AM*ADP -->AM.ADP), ATP isomerization (AM+ATP-->AM*ATP), and with cross-bridge detachment. Force of the AM state agreed well with force measured after induction of the rigor state, indicating that the AM state is a close approximation of the rigor state. The stiffness results obtained as functions of MgATP, MgADP, and Pi concentrations were generally consistent with the cross-bridge scheme.  相似文献   
9.
The human homologue of Drosophila Toll (hToll), also called Toll-like receptor 4 (TLR4), is a recently cloned receptor of the IL-1/Toll receptor family. Interestingly, the TLR4 gene has been localized to the same region to which the Lps locus (endotoxin unresponsive gene locus) is mapped. To examine the role of TLR4 in LPS responsiveness, we have generated mice lacking TLR4. Macrophages and B cells from TLR4-deficient mice did not respond to LPS. All these manifestations were quite similar to those of LPS-hyporesponsive C3H/HeJ mice. Furthermore, C3H/HeJ mice have, in the cytoplasmic portion of TLR4, a single point mutation of the amino acid that is highly conserved among the IL-1/Toll receptor family. Overexpression of wild-type TLR4 but not the mutant TLR4 from C3H/HeJ mice activated NF-kappaB. Taken together, the present study demonstrates that TLR4 is the gene product that regulates LPS response.  相似文献   
10.
Two DCM mutants (E40K and E54K) of tropomyosin (Tm) were examined using the thin-filament extraction/reconstitu­tion technique. The effects of the Ca2+, ATP, phos­phate (Pi), and ADP concentrations on isometric tension and its transients were studied at 25°C, and the results were com­pared to those for the WT protein. Our results indicate that both E40K and E54K have a significantly lower T HC (high Ca2+ ten­sion at pCa 4.66) (E40K: 1.21±0.06 T a, ±SEM, N = 34; E54K: 1.24±0.07 T a, N = 28), a significantly lower T LC (low- Ca2+ tension at pCa 7.0) (E40K: 0.07±0.02 T a, N = 34; E54K: 0.06±0.02 T a, N = 28), and a significantly lower T act (Ca2+ activatable tension) (T act = T HC–TLC, E40K: 1.15±0.08 T a, N = 34; E54K: 1.18±0.06 T a, N = 28) than WT (T HC = 1.53±0.07 T a, T LC = 0.12±0.01 T a, T act = 1.40±0.07 T a, N = 25). All tensions were normalized to T a ( = 13.9±0.8 kPa, N = 57), the ten­sion of actin-filament reconstituted cardiac fibers (myocardium) under the standard activating conditions. The Ca2+ sensitivity (pCa50) of E40K (5.23±0.02, N = 34) and E54K (5.24±0.03, N = 28) was similar to that of the WT protein (5.26±0.03, N = 25). The cooper­a­tivity increased significantly in E54K (3.73±0.25, N = 28) compared to WT (2.80±0.17, N = 25). Seven kinetic constants were deduced using sinusoidal analysis at pCa 4.66. These results enabled us to calculate the cross-bridge distribution in the strongly attached states, and thereby deduce the force/cross-bridge. The results indicate that the force/cross-bridge is ∼15% less in E54K than WT, but remains similar to that of the WT protein in the case of E40K. We conclude that over-inhibition of the actomyosin interaction by E40K and E54K Tm mutants leads to a decreased force-generating ability at systole, which is the main mechanism underlying the early pathogenesis of DCM.  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