全文获取类型
收费全文 | 3913篇 |
免费 | 184篇 |
国内免费 | 2篇 |
出版年
2022年 | 13篇 |
2021年 | 32篇 |
2020年 | 20篇 |
2019年 | 30篇 |
2018年 | 51篇 |
2017年 | 31篇 |
2016年 | 52篇 |
2015年 | 110篇 |
2014年 | 132篇 |
2013年 | 257篇 |
2012年 | 259篇 |
2011年 | 245篇 |
2010年 | 147篇 |
2009年 | 133篇 |
2008年 | 250篇 |
2007年 | 250篇 |
2006年 | 241篇 |
2005年 | 263篇 |
2004年 | 233篇 |
2003年 | 261篇 |
2002年 | 282篇 |
2001年 | 51篇 |
2000年 | 59篇 |
1999年 | 52篇 |
1998年 | 73篇 |
1997年 | 45篇 |
1996年 | 43篇 |
1995年 | 45篇 |
1994年 | 27篇 |
1993年 | 33篇 |
1992年 | 35篇 |
1991年 | 37篇 |
1990年 | 32篇 |
1989年 | 26篇 |
1988年 | 24篇 |
1987年 | 22篇 |
1986年 | 21篇 |
1985年 | 25篇 |
1984年 | 21篇 |
1983年 | 13篇 |
1982年 | 17篇 |
1981年 | 18篇 |
1980年 | 10篇 |
1979年 | 8篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1976年 | 7篇 |
1975年 | 10篇 |
1974年 | 5篇 |
1971年 | 9篇 |
排序方式: 共有4099条查询结果,搜索用时 15 毫秒
991.
992.
Rafiee P Shi Y Pritchard KA Ogawa H Eis AL Komorowski RA Fitzpatrick CM Tweddell JS Litwin SB Mussatto K Jaquiss RD Baker JE 《The Journal of biological chemistry》2003,278(44):43636-43644
Many infants who undergo cardiac surgery have a congenital cyanotic defect where the heart is chronically perfused with hypoxemic blood. Infant hearts adapt to chronic hypoxemia by activation of intracellular protein kinase signal transduction pathways. However, the involvement of heat shock protein 70 in adaptation to chronic hypoxemia and its role in protein kinase signaling pathways is unknown. We determined expression of message and subcellular protein distribution for inducible (Hsp70i) and constitutive heat shock protein 70 (Hsc70) in chronically hypoxic and normoxic infant human and rabbit hearts and their relationship to protein kinases. In chronically hypoxic human and rabbit hearts message levels for Hsp70i were elevated 4- to 5-fold compared with normoxic hearts, Hsp70i protein was redistributed from the particulate to the cytosolic fraction. In normoxic infants Hsp70i protein was distributed almost equally between the cytosolic and particulate fractions. Hsc70 message and subcellular distribution of Hsc70 protein were unaffected by chronic hypoxia. We then determined if protein kinases influence Hsp70i protein subcellular distribution. In rabbit hearts SB203580 and chelerythrine reduced Hsp70i message levels, whereas SB203580, chelerythrine, and curcumin reversed the subcellular redistribution of Hsp70i protein caused by chronic hypoxia, with no effect in normoxic hearts, indicating regulation of Hsp70i message and subcellular distribution of Hsp70i protein in chronically hypoxic rabbit hearts is influenced by protein kinase C and mitogen-activated protein kinases, specifically p38 MAPK and JNK. We conclude the Hsp70 signal transduction pathway plays an important role in adaptation of infant human and rabbit hearts to chronic hypoxemia. 相似文献
993.
994.
Busch A Engemann S Lurz R Okazawa H Lehrach H Wanker EE 《The Journal of biological chemistry》2003,278(42):41452-41461
Aggregation of huntingtin (htt) in neuronal inclusions is associated with the development of Huntington's disease (HD). Previously, we have shown that mutant htt fragments with polyglutamine (polyQ) tracts in the pathological range (>37 glutamines) form SDS-resistant aggregates with a fibrillar morphology, whereas wild-type htt fragments with normal polyQ domains do not aggregate. In this study we have investigated the co-aggregation of mutant and wild-type htt fragments. We found that mutant htt promotes the aggregation of wild-type htt, causing the formation of SDS-resistant co-aggregates with a fibrillar morphology. Conversely, mutant htt does not promote the fibrillogenesis of the polyQ-containing protein NOCT3 or the polyQ-binding protein PQBP1, although these proteins are recruited into inclusions containing mutant htt aggregates in mammalian cells. The formation of mixed htt fibrils is a highly selective process that not only depends on polyQ tract length but also on the surrounding amino acid sequence. Our data suggest that mutant and wild-type htt fragments may also co-aggregate in neurons of HD patients and that a loss of wild-type htt function may contribute to HD pathogenesis. 相似文献
995.
Ohashi K Osuga J Tozawa R Kitamine T Yagyu H Sekiya M Tomita S Okazaki H Tamura Y Yahagi N Iizuka Y Harada K Gotoda T Shimano H Yamada N Ishibashi S 《The Journal of biological chemistry》2003,278(44):42936-42941
The endoplasmic reticulum (ER) enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which converts HMG-CoA to mevalonate, catalyzes the ratelimiting step in cholesterol biosynthesis. Because this mevalonate pathway also produces several non-sterol isoprenoid compounds, the level of HMG-CoA reductase activity may coordinate many cellular processes and functions. We used gene targeting to knock out the mouse HMG-CoA reductase gene. The heterozygous mutant mice (Hmgcr+/-) appeared normal in their development and gross anatomy and were fertile. Although HMG-CoA reductase activities were reduced in Hmgcr+/- embryonic fibroblasts, the enzyme activities and cholesterol biosynthesis remained unaffected in the liver from Hmgcr+/- mice, suggesting that the haploid amount of Hmgcr gene is not rate-limiting in the hepatic cholesterol homeostasis. Consistently, plasma lipoprotein profiles were similar between Hmgcr+/- and Hmgcr+/+ mice. In contrast, the embryos homozygous for the Hmgcr mutant allele were recovered at the blastocyst stage, but not at E8.5, indicating that HMG-CoA reductase is crucial for early development of the mouse embryos. The lethal phenotype was not completely rescued by supplementing the dams with mevalonate. Although it has been postulated that a second, peroxisome-specific HMG-CoA reductase could substitute for the ER reductase in vitro, we speculate that the putative peroxisomal reductase gene, if existed, does not fully compensate for the lack of the ER enzyme at least in embryogenesis. 相似文献
996.
Antagonist of secondary lymphoid-tissue chemokine (CCR ligand 21) prevents the development of chronic graft-versus-host disease in mice 总被引:5,自引:0,他引:5
Sasaki M Hasegawa H Kohno M Inoue A Ito MR Fujita S 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(1):588-596
The use of receptor antagonists for chemokines is an alternative approach to blocking chemokine actions and has the potential to provide novel therapeutics. We determined the receptor antagonist properties of murine N-terminally truncated secondary lymphoid tissue chemokine (SLC)/6Ckine/CCR ligand 21 analogs and evaluated the preventive effects of SLC antagonists on chronic graft-vs-host disease (GVHD) in a murine model by blocking the homing of donor CCR7-expressing T cells into the recipient's lymphoid organs. SLC analogs truncated >4 aa residues from the N terminus showed a loss of chemotaxis and Ca2+ influx of CCR7-expressing cells and also inhibited SLC-stimulated chemotaxis and SLC-induced Ca2+ influx completely. To determine whether SLC antagonist inhibits the development of chronic GVHD, chronic GVHD was induced by injecting DBA/2 spleen cells into (C57BL/6 x DBA/2) F1 mice. Total numbers of spleen cells and host B cells, serum levels of IgE, and of total IgG and IgG1 of anti-DNA Abs in SLC antagonist-treated GVHD mice were significantly lower than those in control PBS-treated GVHD mice. This was due to a reduction in the levels of activated donor CD4+ T cells and a decrease in IL-4 production, resulting in a reduction in the numbers of activated host B cells. Therefore, our results suggest that SLC antagonist has beneficial effects for the prevention of chronic GVHD. 相似文献
997.
998.
Hadase M Kawasaki T Asada S Kamitani T Kawasaki S Sugihara H 《International journal of cardiovascular interventions》2003,5(2):98-101
The YUMIKO catheter (Goodman, Nagoya, Japan) was recently developed for a left internal mammary artery (IMA) angiography with a right radial or brachial approach. The present authors experienced an interesting case where the YUMIKO catheter was useful for a right IMA angiography via a right brachial artery. A 53-year-old man with bilateral IMA grafts underwent follow-up coronary angiography via a right brachial artery. Native coronary artery and left IMA angiography were performed without difficulty using the Judkins Right and Left and YUMIKO catheters. Angiography of the right IMA was attempted with the Judkins Right catheter and IMA catheter, resulting in a nonselective angiogram with poor imaging. The YUMIKO catheter, however, enabled smooth cannulation to the right IMA and provided good images of the selective right IMA angiography. 相似文献
999.
Assembly of the coat protein I (COPI) vesicle coat is controlled by the small GTPase ADP ribosylation factor 1 (ARF1) and its GTPase-activating protein, ARFGAP1. Here, we investigate the diffusional behaviours of coatomer, the main component of the coat, and also those of ARF1 and ARFGAP1. Using fluorescence-correlation spectroscopy, we found that most ARF1 and ARFGAP1 molecules are highly mobile in the cytosol (diffusion constant D ≈ 15 μm2 s−1), whereas coatomer diffuses 5–10 times more slowly than expected (D ≈ 1 μm2 s−1). This slow diffusion causes diffusion-limited binding kinetics to Golgi membranes, which, in FRAP (fluorescence recovery after photobleaching) experiments, translates into a twofold slower binding rate. The addition of aluminium fluoride locks coatomer onto Golgi membranes and also decreases the binding kinetics of both ARF1 and ARFGAP1, suggesting that these proteins function in concert to mediate sorting and vesicle formation. 相似文献
1000.
Although semaphorins were identified originally as guidance cues for developing neuronal axons, accumulating evidence indicates that several semaphorins are expressed also in the immune system. SEMA4D (CD100), which is expressed constitutively by T cells, enhances the activation of B cells and dendritic cells (DCs) through its cell-surface receptor, CD72. SEMA4A, which is expressed by DCs, is involved in the activation of T cells through interactions with TIM2. So, these semaphorins seem to function in the reciprocal stimulation of T cells and antigen-presenting cells (APCs). Emerging evidence indicates that additional semaphorins and related molecules are involved in T-cell-APC interactions also. 相似文献