全文获取类型
收费全文 | 31721篇 |
免费 | 2778篇 |
国内免费 | 22篇 |
出版年
2023年 | 163篇 |
2022年 | 369篇 |
2021年 | 785篇 |
2020年 | 424篇 |
2019年 | 559篇 |
2018年 | 666篇 |
2017年 | 543篇 |
2016年 | 968篇 |
2015年 | 1652篇 |
2014年 | 1732篇 |
2013年 | 2041篇 |
2012年 | 2661篇 |
2011年 | 2708篇 |
2010年 | 1644篇 |
2009年 | 1367篇 |
2008年 | 2021篇 |
2007年 | 2000篇 |
2006年 | 1940篇 |
2005年 | 1666篇 |
2004年 | 1688篇 |
2003年 | 1481篇 |
2002年 | 1446篇 |
2001年 | 287篇 |
2000年 | 208篇 |
1999年 | 269篇 |
1998年 | 300篇 |
1997年 | 218篇 |
1996年 | 198篇 |
1995年 | 174篇 |
1994年 | 150篇 |
1993年 | 146篇 |
1992年 | 120篇 |
1991年 | 145篇 |
1990年 | 106篇 |
1989年 | 95篇 |
1988年 | 84篇 |
1987年 | 69篇 |
1986年 | 84篇 |
1985年 | 95篇 |
1984年 | 94篇 |
1983年 | 93篇 |
1982年 | 113篇 |
1981年 | 111篇 |
1980年 | 88篇 |
1979年 | 61篇 |
1978年 | 47篇 |
1977年 | 45篇 |
1976年 | 49篇 |
1975年 | 47篇 |
1974年 | 46篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
A modification of the trap assay (Woodard et al., 1989) was used to evaluate the response of Drosophila melanogaster (Meigen) to food media containing menthol. Dose-response curves for flies to mentholic foods were produced for flies that had been pre-exposed to menthol, during development and adult life, and flies that had not been exposed to menthol before the assay. Mentholic food media were less attractive to Drosophila than plain food medium. Rearing flies on a medium containing menthol reduced their aversion to some concentrations of menthol. The rearing effect was not simply due to lowered general activity levels resulting from developing in a medium containing menthol. There was a threshold concentration of menthol in the rearing medium below which we found no induced behavioural change. 相似文献
52.
Scaling of metabolic rate with body mass and temperature in teleost fish 总被引:27,自引:0,他引:27
53.
54.
55.
Investigation of kinase-related processes often uses pharmacological inhibition to reveal pathways in which kinases are involved. However, one concern about using such kinase inhibitors is their potential lack of specificity. Here, we report that the calcium–calmodulin-dependent kinase II (CaMKII) inhibitor CK59 inhibited multiple voltage-gated calcium channels, including the L-type channel during depolarization in a dose-dependent manner. The use of another CaMKII inhibitor, cell-permeable autocamtide-2 related inhibitory peptide II (Ant-AIP-II), failed to similarly decrease calcium current or entry in hippocampal cultures, as shown by ratiometric calcium imaging and whole-cell patch clamp electrophysiology. Notably, inhibition due to CK59 was reversible; washout of the drug brought calcium levels back to control values upon depolarization. Furthermore, the IC50 for CK59 was approximately 50 μM, which is only fivefold larger than the reported IC50 values for CaMKII inhibition. Similar nonspecific actions of other CaMKII inhibitors KN93 and KN62 have previously been reported. In the case of all three kinase inhibitors, the IC50 for calcium current inhibition falls near that of CaMKII inhibition. Our findings demonstrate that CK59 attenuates activity of voltage-gated calcium channels, and thus provide more evidence for caution when relying on pharmacological inhibition to examine kinase-dependent phenomena. 相似文献
56.
Comparative phylogeography of two co‐distributed but ecologically distinct rainbowfishes of far‐northern Australia
下载免费PDF全文
![点击此处可从《Journal of Biogeography》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Andrew T. Mather Jeffrey O. Hanson Lisa C. Pope Cynthia Riginos 《Journal of Biogeography》2018,45(1):127-141
Aim
To test the influence of historical and contemporary environment in shaping the genetic diversity of freshwater fauna we contrast genetic structure in two co‐distributed, but ecologically distinct, rainbowfish; a habitat generalist (Melanotaenia splendida) and a habitat specialist (M. trifasciata).Location
Fishes were sampled from far northern Australia (Queensland and Northern Territory).Methods
We used sequence data from one mitochondrial gene and one nuclear gene to investigate patterns of genetic diversity in M. splendida and M. trifasciata to determine how differences in habitat preference and historical changes in drainage boundaries affected patterns of connectivity.Results
Melanotaenia splendida showed high levels of genetic diversity and little population structure across its range. In contrast, M. trifasciata showed high levels of population structure. Whereas phylogeographic patterns differed, both species showed a strong relationship between geographical distance and genetic differentiation between populations. Melanotaenia splendida showed a shallower relationship with geographical distance, and genetic differentiation was best explained by stream length and a lower scaled ocean distance (11.98 times coast length). For M. trifasciata, genetic differentiation was best explained by overwater distance between catchments and ocean distance scaled at 1.16 × 106 times coast length.Main conclusions
Connectivity of freshwater populations inhabiting regions periodically interconnected during glacial periods appears to have been affected by ecological differences between species. Species‐specific differences are epitomized here by the contrast between co‐distributed congeners with different habitat requirements: for the habitat generalist, M. splendida, there was evidence for greater historical genetic connectivity with oceans as a weaker barrier to gene exchange in contrast with the habitat specialist, M. trifasciata. 相似文献57.
Carwyn Davies Linda A Hogarth Karen L Mackenzie Andrew G Hall Richard B Lock 《Cell cycle (Georgetown, Tex.)》2015,14(22):3602-3612
p21WAF1 is a well-characterized mediator of cell cycle arrest and may also modulate chemotherapy-induced cell death. The role of p21WAF1 in drug-induced cell cycle arrest and apoptosis of acute lymphoblastic leukemia (ALL) cells was investigated using p53-functional patient-derived xenografts (PDXs), in which p21WAF1 was epigenetically silenced in T-cell ALL (T-ALL), but not in B-cell precursor (BCP)-ALL PDXs. Upon exposure to diverse cytotoxic drugs, T-ALL PDX cells exhibited markedly increased caspase-3/7 activity and phosphatidylserine (PS) externalization on the plasma membrane compared with BCP-ALL cells. Despite dramatic differences in apoptotic characteristics between T-ALL and BCP-ALL PDXs, both ALL subtypes exhibited similar cell death kinetics and were equally sensitive to p53-inducing drugs in vitro, although T-ALL PDXs were significantly more sensitive to the histone deacetylase inhibitor vorinostat. Transient siRNA suppression of p21WAF1 in the BCP-ALL 697 cell line resulted in a moderate depletion of the cell fraction in G1 phase and marked increase in PS externalization following exposure to etoposide. Furthermore, stable lentiviral p21WAF1 silencing in the BCP-ALL Nalm-6 cell line accelerated PS externalization and cell death following exposure to etoposide and vorinostat, supporting previous findings. Finally, the Sp1 inhibitor, terameprocol, inhibited p21WAF1 expression in Nalm-6 cells exposed to vorinostat and also partially augmented vorinostat-induced cell death. Taken together, these findings demonstrate that p21WAF1 regulates the early stages of drug-induced apoptosis in ALL cells and significantly modulates their sensitivity to vorinostat. 相似文献
58.
Nirmal Mazumder Rodney K. Lyn Ragunath Singaravelu Andrew Ridsdale Douglas J. Moffatt Chih-Wei Hu Han-Ruei Tsai John McLauchlan Albert Stolow Fu-Jen Kao John Paul Pezacki 《PloS one》2013,8(6)
Hepatitis C virus (HCV) co-opts hepatic lipid pathways to facilitate its pathogenesis. The virus alters cellular lipid biosynthesis and trafficking, and causes an accumulation of lipid droplets (LDs) that gives rise to hepatic steatosis. Little is known about how these changes are controlled at the molecular level, and how they are related to the underlying metabolic states of the infected cell. The HCV core protein has previously been shown to independently induce alterations in hepatic lipid homeostasis. Herein, we demonstrate, using coherent anti-Stokes Raman scattering (CARS) microscopy, that expression of domain 2 of the HCV core protein (D2) fused to GFP is sufficient to induce an accumulation of larger lipid droplets (LDs) in the perinuclear region. Additionally, we performed fluorescence lifetime imaging of endogenous reduced nicotinamide adenine dinucleotides [NAD(P)H], a key coenzyme in cellular metabolic processes, to monitor changes in the cofactor’s abundance and conformational state in D2-GFP transfected cells. When expressed in Huh-7 human hepatoma cells, we observed that the D2-GFP induced accumulation of LDs correlated with an increase in total NAD(P)H fluorescence and an increase in the ratio of free to bound NAD(P)H. This is consistent with an approximate 10 fold increase in cellular NAD(P)H levels. Furthermore, the lifetimes of bound and free NAD(P)H were both significantly reduced – indicating viral protein-induced alterations in the cofactors’ binding and microenvironment. Interestingly, the D2-expressing cells showed a more diffuse localization of NAD(P)H fluorescence signal, consistent with an accumulation of the co-factor outside the mitochondria. These observations suggest that HCV causes a shift of metabolic control away from the use of the coenzyme in mitochondrial electron transport and towards glycolysis, lipid biosynthesis, and building of new biomass. Overall, our findings demonstrate that HCV induced alterations in hepatic metabolism is tightly linked to alterations in NAD(P)H functional states. 相似文献
59.
60.