全文获取类型
收费全文 | 7001篇 |
免费 | 434篇 |
专业分类
7435篇 |
出版年
2023年 | 57篇 |
2022年 | 95篇 |
2021年 | 176篇 |
2020年 | 114篇 |
2019年 | 134篇 |
2018年 | 199篇 |
2017年 | 143篇 |
2016年 | 228篇 |
2015年 | 376篇 |
2014年 | 351篇 |
2013年 | 526篇 |
2012年 | 577篇 |
2011年 | 547篇 |
2010年 | 346篇 |
2009年 | 325篇 |
2008年 | 391篇 |
2007年 | 388篇 |
2006年 | 389篇 |
2005年 | 362篇 |
2004年 | 326篇 |
2003年 | 287篇 |
2002年 | 287篇 |
2001年 | 47篇 |
2000年 | 33篇 |
1999年 | 45篇 |
1998年 | 61篇 |
1997年 | 65篇 |
1996年 | 33篇 |
1995年 | 51篇 |
1994年 | 42篇 |
1993年 | 37篇 |
1992年 | 25篇 |
1991年 | 34篇 |
1990年 | 16篇 |
1989年 | 19篇 |
1988年 | 24篇 |
1987年 | 16篇 |
1986年 | 9篇 |
1985年 | 14篇 |
1984年 | 31篇 |
1983年 | 17篇 |
1982年 | 18篇 |
1981年 | 23篇 |
1980年 | 23篇 |
1979年 | 17篇 |
1978年 | 17篇 |
1977年 | 11篇 |
1976年 | 11篇 |
1974年 | 9篇 |
1965年 | 8篇 |
排序方式: 共有7435条查询结果,搜索用时 0 毫秒
991.
992.
Protein phosphorylation plays a central role in many signal transduction pathways that mediate biological processes. Novel quantitative mass spectrometry-based methods have recently revealed phosphorylation dynamics in animals, yeast, and plants. These methods are important for our understanding of how differential phosphorylation participates in translating distinct signals into proper physiological responses, and shifted research towards screening for potential cancer therapies and in-depth analysis of phosphoproteomes. In this review, we aim to describe current progress in quantitative phosphoproteomics. This emerging field has changed numerous static pathways into dynamic signaling networks, and revealed protein kinase networks that underlie adaptation to environmental stimuli. Mass spectrometry enables high-throughput and high-quality analysis of differential phosphorylation at a site-specific level. Although determination of differential phosphorylation between treatments is analogous to detecting differential gene expression, the large body of statistical techniques that has been developed for analysis of differential gene expression is not generally applied for detecting differential phosphorylation. We suggest possible improvements for analysis of quantitative phosphorylation by increasing the number of biological replicates and adapting statistical tests used for gene expression profiling and widely implemented in freely available software tools. 相似文献
993.
The present paper will present a survey on features of a number of non-specialized off-the-shelf JPEG2000 viewers, seen from the point of view of digital microscopy. Selected viewers were tested within a number of usage scenarios, including: i) open a conformance test JPEG2000 file; ii) open a large JPEG2000 file; iii) moving from one point to another; iv) changing resolution/magnification. For each scenario, data recorded included: successful or unsuccessful operation; time needed for conclusion; occasional problems.Preliminary results demonstrate that JPEG2000 conformance as stated by many viewers is only limited to some of the possibilities of the JPEG2000 standard, in particular for what regards file size. 相似文献
994.
995.
996.
997.
998.
999.
Ruvolo VR Kurinna SM Karanjeet KB Schuster TF Martelli AM McCubrey JA Ruvolo PP 《The Journal of biological chemistry》2008,283(51):35474-35485
Protein phosphatase 2A (PP2A) is a heterotrimer comprising catalytic, scaffold, and regulatory (B) subunits. There are at least 21 B subunit family members. Thus PP2A is actually a family of enzymes defined by which B subunit is used. The B56 family member B56alpha is a phosphoprotein that regulates dephosphorylation of BCL2. The stress kinase PKR has been shown to phosphorylate B56alpha at serine 28 in vitro, but it has been unclear how PKR might regulate the BCL2 phosphatase. In the present study, PKR regulation of B56alpha in REH cells was examined, because these cells exhibit robust BCL2 phosphatase activity. PKR was found to be basally active in REH cells as would be predicted if the kinase supports B56alpha-mediated dephosphorylation of BCL2. Suppression of PKR promoted BCL2 phosphorylation with concomitant loss of B56alpha phosphorylation at serine 28 and inhibition of mitochondrial PP2A activity. PKR supports stress signaling in REH cells, as suppression of PKR promoted chemoresistance to etoposide. Suppression of PKR promoted B56alpha proteolysis, which could be blocked by a proteasome inhibitor. However, the mechanism by which PKR supports B56alpha protein does not involve PKR-mediated phosphorylation of the B subunit at serine 28 but may involve eIF2alpha activation of AKT. Phosphorylation of serine 28 by PKR promotes mitochondrial localization of B56alpha, because wild-type but not mutant S28A B56alpha promoted mitochondrial PP2A activity. Cells expressing wild-type B56alpha but not S28A B56alpha were sensitized to etoposide. These results suggest that PKR regulates B56alpha-mediated PP2A signaling in REH cells. 相似文献
1000.
Chloride Is essential for capacitation and for the capacitation-associated increase in tyrosine phosphorylation 总被引:1,自引:0,他引:1
Wertheimer EV Salicioni AM Liu W Trevino CL Chavez J Hernández-González EO Darszon A Visconti PE 《The Journal of biological chemistry》2008,283(51):35539-35550
After epididymal maturation, sperm capacitation, which encompasses a complex series of molecular events, endows the sperm with the ability to fertilize an egg. This process can be mimicked in vitro in defined media, the composition of which is based on the electrolyte concentration of the oviductal fluid. It is well established that capacitation requires Na(+), HCO(3)(-), Ca(2+), and a cholesterol acceptor; however, little is known about the function of Cl(-) during this important process. To determine whether Cl(-), in addition to maintaining osmolarity, actively participates in signaling pathways that regulate capacitation, Cl(-) was replaced by either methanesulfonate or gluconate two nonpermeable anions. The absence of Cl(-) did not affect sperm viability, but capacitation-associated processes such as the increase in tyrosine phosphorylation, the increase in cAMP levels, hyperactivation, the zona pellucidae-induced acrosome reaction, and most importantly, fertilization were abolished or significantly reduced. Interestingly, the addition of cyclic AMP agonists to sperm incubated in Cl(-)-free medium rescued the increase in tyrosine phosphorylation and hyperactivation suggesting that Cl(-) acts upstream of the cAMP/protein kinase A signaling pathway. To investigate Cl(-) transport, sperm incubated in complete capacitation medium were exposed to a battery of anion transport inhibitors. Among them, bumetanide and furosemide, two blockers of Na(+)/K(+)/Cl(-) cotransporters (NKCC), inhibited all capacitation-associated events, suggesting that these transporters may mediate Cl(-) movements in sperm. Consistent with these results, Western blots using anti-NKCC1 antibodies showed the presence of this cotransporter in mature sperm. 相似文献