全文获取类型
收费全文 | 5175篇 |
免费 | 619篇 |
国内免费 | 1篇 |
出版年
2022年 | 41篇 |
2021年 | 76篇 |
2020年 | 42篇 |
2019年 | 47篇 |
2018年 | 65篇 |
2017年 | 67篇 |
2016年 | 109篇 |
2015年 | 165篇 |
2014年 | 185篇 |
2013年 | 240篇 |
2012年 | 306篇 |
2011年 | 284篇 |
2010年 | 192篇 |
2009年 | 143篇 |
2008年 | 231篇 |
2007年 | 230篇 |
2006年 | 222篇 |
2005年 | 211篇 |
2004年 | 177篇 |
2003年 | 217篇 |
2002年 | 187篇 |
2001年 | 185篇 |
2000年 | 167篇 |
1999年 | 143篇 |
1998年 | 92篇 |
1997年 | 71篇 |
1996年 | 69篇 |
1995年 | 73篇 |
1994年 | 55篇 |
1993年 | 61篇 |
1992年 | 113篇 |
1991年 | 94篇 |
1990年 | 91篇 |
1989年 | 78篇 |
1988年 | 83篇 |
1987年 | 55篇 |
1986年 | 85篇 |
1985年 | 73篇 |
1984年 | 52篇 |
1983年 | 57篇 |
1982年 | 47篇 |
1981年 | 47篇 |
1980年 | 54篇 |
1979年 | 44篇 |
1978年 | 41篇 |
1977年 | 30篇 |
1976年 | 41篇 |
1973年 | 39篇 |
1972年 | 31篇 |
1968年 | 34篇 |
排序方式: 共有5795条查询结果,搜索用时 31 毫秒
991.
Jensen OP Hansson S Didrikas T Stockwell JD Hrabik TR Axenrot T Kitchell JF 《Journal of fish biology》2011,79(2):449-465
This study is the first to characterize temporal changes in blood chemistry of individuals from one population of male sockeye salmon Oncorhynchus nerka during the final 6 weeks of sexual maturation and senescence in the freshwater stage of their spawning migration. Fish that died before the start of their historic mean spawning period (c. 5 November) were characterized by a 20-40% decrease in plasma osmolality, chloride and sodium, probably representing a complete loss of osmoregulatory ability. As fish became moribund, they were further characterized by elevated levels of plasma cortisol, lactate and potassium. Regressions between time to death and plasma chloride (8 October: P < 0·001; 15 October: P < 0·001) indicate that plasma chloride was a strong predictor of longevity in O. nerka. That major plasma ion levels started to decline 2-10 days (mean of 6 days) before fish became moribund, and before other stress, metabolic or reproductive hormone variables started to change, suggests that a dysfunctional osmoregulatory system may initiate rapid senescence and influence other physiological changes (i.e. elevated stress and collapsed reproductive hormones) which occur as O. nerka die on spawning grounds. 相似文献
992.
Rasmussen SB Horan KA Holm CK Stranks AJ Mettenleiter TC Simon AK Jensen SB Rixon FJ He B Paludan SR 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(10):5268-5276
Autophagy has been established as a player in host defense against viruses. The mechanisms by which the host induces autophagy during infection are diverse. In the case of HSV type 1 (HSV-1), dsRNA-dependent protein kinase is essential for induction of autophagy in fibroblasts through phosphorylation of eukaryotic initiation factor 2α (eIF2α). HSV-1 counteracts autophagy via ICP34.5, which dephosphorylates eIF2α and inhibits Beclin 1. Investigation of autophagy during HSV-1 infection has largely been conducted in permissive cells, but recent work suggests the existence of a eIF2α-independent autophagy-inducing pathway in nonpermissive cells. To clarify and further characterize the existence of a novel autophagy-inducing pathway in nonpermissive cells, we examined different HSV and cellular components in murine myeloid cells for their role in autophagy. We demonstrate that HSV-1-induced autophagy does not correlate with phosphorylation of eIF2α, is independent of functional dsRNA-dependent protein kinase, and is not antagonized by ICP34.5. Autophagy was activated independent of viral gene expression, but required viral entry. Importantly, we found that the presence of genomic DNA in the virion was essential for induction of autophagy and, conversely, that transfection of HSV-derived DNA induced microtubule-associated protein 1 L chain II formation, a marker of autophagy. This occurred through a mechanism dependent on stimulator of IFN genes, an essential component for the IFN response to intracellular DNA. Finally, we observed that HSV-1 DNA was present in the cytosol devoid of capsid material following HSV-1 infection of dendritic cells. Thus, our data suggest that HSV-1 genomic DNA induces autophagy in nonpermissive cells in a stimulator of IFN gene-dependent manner. 相似文献
993.
Castro-Perez J Previs SF McLaren DG Shah V Herath K Bhat G Johns DG Wang SP Mitnaul L Jensen K Vreeken R Hankemeier T Roddy TP Hubbard BK 《Journal of lipid research》2011,52(1):159-169
High resolution LC/MS-MS and LC/APPI-MS methods have been established for the quantitation of flux in the turnover of cholesterol and cholesterol ester. Attention was directed toward quantifying the monoisotopic mass (M0) and that of the singly deuterated labeled (M+1) isotope. A good degree of isotopic dynamic range has been achieved by LC/MS-MS ranging from 3-4 orders of magnitude. Correlation between the linearity of GC/MS and LC atmospheric pressure photoionization (APPI)-MS are complimentary (r2 = 0.9409). To prove the viability of this particular approach, male C57Bl/6 mice on either a high carbohydrate (HC) or a high fat (HF) diet were treated with 2H2O for 96 h. Gene expression analysis showed an increase in the activity of stearoyl-CoA desaturase (Scd1) in the HC diet up to 69-fold (P < 0.0008) compared with the HF diet. This result was supported by the quantitative flux measurement of the isotopic incorporation of 2H into the respective cholesterol and cholesterol ester (CE) pools. We concluded that it is possible to readily obtain static and dynamic measurement of cholesterol and CEs in vivo by coupling novel LC/MS methods with stable isotope-based protocols. 相似文献
994.
995.
Farrell HE Abraham AM Cardin RD Sparre-Ulrich AH Rosenkilde MM Spiess K Jensen TH Kledal TN Davis-Poynter N 《Journal of virology》2011,85(12):6091-6095
The human cytomegalovirus (CMV) proteins US28 and UL33 are homologous to chemokine receptors (CKRs). Knockout of the mouse CMV M33 protein (UL33 homologue) results in substantial attenuation of salivary gland infection/replication and reduced efficiency of reactivation from tissue explants. M33-mediated G protein-coupled signaling is critical for the salivary gland phenotype. In this report, we demonstrate that US28 and (to a lesser degree) UL33 restore reactivation from tissue explants and partially restore replication in salivary glands (compared to a signaling-deficient M33 mutant). These studies provide a novel small animal model for evaluation of therapies targeting the human CMV CKRs. 相似文献
996.
Jensen MH Sukumaran M Johnson CM Greger IH Neuweiler H 《Journal of molecular biology》2011,414(1):96-105
Ionotropic glutamate receptors (iGluRs) mediate excitatory neurotransmission in the central nervous system and play key roles in brain development and disease. iGluRs have two distinct extracellular domains, but the functional role of the distal N-terminal domain (NTD) is poorly understood. Crystal structures of the NTD from some non-N-methyl-d-aspartate (NMDA) iGluRs are consistent with a rigid body that facilitates receptor assembly but suggest an additional dynamic role that could modulate signaling. Here, we moved beyond spatial and temporal limitations of conventional protein single-molecule spectroscopy by employing correlation analysis of extrinsic oxazine fluorescence fluctuations. We observed nanosecond (ns)-to-microsecond (μs) motions of loop segments and helices within a region of an AMPA-type iGluR NTD, which has been identified previously to be structurally variable. Our data reveal that the AMPA receptor NTD undergoes rapid conformational fluctuations, suggesting an inherent allosteric capacity for this domain in addition to its established assembly function. 相似文献
997.
998.
Kjaersgaard T Jensen MK Christiansen MW Gregersen P Kragelund BB Skriver K 《The Journal of biological chemistry》2011,286(41):35418-35429
999.
1000.
Pham L Beyer K Jensen ED Rodriguez JS Davydova J Yamamoto M Petryk A Gopalakrishnan R Mansky KC 《Journal of cellular biochemistry》2011,112(3):793-803
Bone morphogenetic proteins (BMPs) have been shown to regulate both osteoblasts and osteoclasts. We previously reported that BMP2 could directly enhance RANKL-mediated osteoclast differentiation by increasing the size and number of osteoclasts. Similarly, genetic deletion of the BMP antagonist Twisted gastrulation (TWSG1) in mice, resulted in an enhancement of osteoclast formation, activity and osteopenia. This was accompanied by increased levels of phosphorylated Smad (pSmad) 1/5/8 in Twsg1(-/-) osteoclasts in vitro. The purpose of this study was to develop an adenoviral vector overexpressing Twsg1 as a means of inhibiting osteoclast activity. We demonstrate that overexpressing TWSG1 in primary osteoclasts decreased the size and number of multinuclear TRAP-positive osteoclasts, expression of osteoclast genes, and resorption ability. Overexpression of TWSG1 did not affect osteoclast proliferation or apoptosis. However, overexpression of TWSG1 decreased the levels of pSmad 1/5/8 in osteoclasts. Addition of exogenous BMP2 to osteoclasts overexpressing TWSG1 rescued the size and levels of pSmad 1/5/8 compared to cultures infected with a control virus. Finally, TWSG1 overexpression in osteoclasts isolated from the Twsg1(-/-) mice rescued size of the osteoclasts while further addition of exogenous BMP2 reversed the effect of TWSG1 overexpression and increased the size of the osteoclasts similar to control virus infected cells. Taken together, we demonstrate that overexpressing TWSG1 in osteoclasts via an adenoviral vector results in inhibition of osteoclastogenesis and may provide a potential therapy for inhibiting osteoclast activity in a localized manner. 相似文献