全文获取类型
收费全文 | 2115篇 |
免费 | 259篇 |
出版年
2021年 | 20篇 |
2019年 | 21篇 |
2018年 | 33篇 |
2017年 | 21篇 |
2016年 | 31篇 |
2015年 | 71篇 |
2014年 | 75篇 |
2013年 | 93篇 |
2012年 | 99篇 |
2011年 | 128篇 |
2010年 | 66篇 |
2009年 | 50篇 |
2008年 | 91篇 |
2007年 | 78篇 |
2006年 | 79篇 |
2005年 | 61篇 |
2004年 | 74篇 |
2003年 | 71篇 |
2002年 | 64篇 |
2001年 | 54篇 |
2000年 | 61篇 |
1999年 | 52篇 |
1998年 | 31篇 |
1997年 | 23篇 |
1996年 | 36篇 |
1995年 | 20篇 |
1994年 | 23篇 |
1993年 | 20篇 |
1992年 | 49篇 |
1991年 | 44篇 |
1990年 | 43篇 |
1989年 | 34篇 |
1988年 | 47篇 |
1987年 | 49篇 |
1986年 | 28篇 |
1985年 | 35篇 |
1984年 | 25篇 |
1983年 | 28篇 |
1982年 | 21篇 |
1981年 | 17篇 |
1980年 | 19篇 |
1979年 | 33篇 |
1978年 | 25篇 |
1977年 | 22篇 |
1975年 | 19篇 |
1974年 | 28篇 |
1972年 | 19篇 |
1970年 | 16篇 |
1968年 | 16篇 |
1967年 | 17篇 |
排序方式: 共有2374条查询结果,搜索用时 437 毫秒
991.
Martha J. Somerman Janice E. Berry Zhila Khalkhali-Ellis Philip Osdoby Robert U. Simpson 《Experimental cell research》1995,216(2)
HL-60 cells, a promyelocytic leukemic cell line, provide a good model for studying the role of adhesion molecules and associated receptors involved in cell differentiation. When exposed to factors such as phorbol esters, these cells grown in suspension differentiate into monocytes and adhere to tissue culture dishes. In this study we showed that HL-60 cells exposed to phorbol esters express osteopontin (OPN), a cell adhesion molecule linked with osteoclast function. Moreover, the timed expression of OPN, in phorbol ester treated cells, was linked to increased cell adhesion. Subsequent to the expression of OPN, an increase in mRNA levels for αV integrin subunit was observed. The αVβ3 integrin, a cell surface receptor found in high concentrations in osteoclasts, is considered to be a receptor for OPN. Furthermore, during differentiation we detected an increase in two cell surface markers specific for osteoclasts, 75B and 121F. This is the first report to demonstrate expression of OPN during differentiation of HL-60 cells, indicating that HL-60 cells can be used as a tool to enhance our understanding as to the role of OPN in cell differentiation. 相似文献
992.
993.
Heaven Oliver‐Kozup Karen H. Martin Diane Schwegler‐Berry Brett J. Green Courtney Betts Arti V. Shinde Livingston Van De Water Slawomir Lukomski 《Molecular microbiology》2013,87(3):672-689
Wounds are known to serve as portals of entry for group A Streptococcus (GAS). Subsequent tissue colonization is mediated by interactions between GAS surface proteins and host extracellular matrix components. We recently reported that the streptococcal collagen‐like protein‐1, Scl1, selectively binds the cellular form of fibronectin (cFn) and also contributes to GAS biofilm formation on abiotic surfaces. One structural feature of cFn, which is predominantly expressed in response to tissue injury, is the presence of a spliced variant containing extra domain A (EDA/EIIIA). We now report that GAS biofilm formation is mediated by the Scl1 interaction with EDA‐containing cFn. Recombinant Scl1 proteins that bound cFn also bound recombinant EDA within the C‐C’ loop region recognized by the α9β1 integrin. The extracellular 2‐D matrix derived from human dermal fibroblasts supports GAS adherence and biofilm formation. Altogether, this work identifies and characterizes a novel molecular mechanism by which GAS utilizes Scl1 to specifically target an extracellular matrix component that is predominantly expressed at the site of injury in order to secure host tissue colonization. 相似文献
994.
Richard J. A. Berry 《BMJ (Clinical research ed.)》1933,1(3768):535-536
995.
Li-shar Huang Peter Lümmen Edward A. Berry 《Biochimica et Biophysica Acta - Proteins and Proteomics》2021,1869(9):140679
The quinone binding site (Q-site) of Mitochondrial Complex II (succinate-ubiquinone oxidoreductase) is the target for a number of inhibitors useful for elucidating the mechanism of the enzyme. Some of these have been developed as fungicides or pesticides, and species-specific Q-site inhibitors may be useful against human pathogens. We report structures of chicken Complex II with six different Q-site inhibitors bound, at resolutions 2.0–2.4 Å. These structures show the common interactions between the inhibitors and their binding site. In every case a carbonyl or hydroxyl oxygen of the inhibitor is H-bonded to Tyr58 in subunit SdhD and Trp173 in subunit SdhB. Two of the inhibitors H-bond Ser39 in subunit SdhC directly, while two others do so via a water molecule. There is a distinct cavity that accepts the 2-substituent of the carboxylate ring in flutolanil and related inhibitors. A hydrophobic “tail pocket” opens to receive a side-chain of intermediate-length inhibitors. Shorter inhibitors fit entirely within the main binding cleft, while the long hydrophobic side chains of ferulenol and atpenin A5 protrude out of the cleft into the bulk lipid region, as presumably does that of ubiquinone. Comparison of mitochondrial and Escherichia coli Complex II shows a rotation of the membrane-anchor subunits by 7° relative to the iron?sulfur protein. This rotation alters the geometry of the Q-site and the H-bonding pattern of SdhB:His216 and SdhD:Asp57. This conformational difference, rather than any active-site mutation, may be responsible for the different inhibitor sensitivity of the bacterial enzyme. 相似文献
996.
997.
Ryan T. Cleary Hongyu Sun Thanhthao Huynh Simon M. Manning Yijun Li Alexander Rotenberg Delia M. Talos Kristopher T. Kahle Michele Jackson Sanjay N. Rakhade Gerard Berry Frances E. Jensen 《PloS one》2013,8(3)
Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na+-K+-2 Cl− cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures. 相似文献
998.
999.
1000.