全文获取类型
收费全文 | 6484篇 |
免费 | 251篇 |
国内免费 | 97篇 |
出版年
2024年 | 6篇 |
2023年 | 51篇 |
2022年 | 78篇 |
2021年 | 112篇 |
2020年 | 95篇 |
2019年 | 170篇 |
2018年 | 157篇 |
2017年 | 122篇 |
2016年 | 126篇 |
2015年 | 148篇 |
2014年 | 256篇 |
2013年 | 393篇 |
2012年 | 231篇 |
2011年 | 310篇 |
2010年 | 159篇 |
2009年 | 260篇 |
2008年 | 319篇 |
2007年 | 335篇 |
2006年 | 301篇 |
2005年 | 250篇 |
2004年 | 254篇 |
2003年 | 226篇 |
2002年 | 205篇 |
2001年 | 150篇 |
2000年 | 150篇 |
1999年 | 147篇 |
1998年 | 141篇 |
1997年 | 125篇 |
1996年 | 134篇 |
1995年 | 136篇 |
1994年 | 131篇 |
1993年 | 112篇 |
1992年 | 113篇 |
1991年 | 114篇 |
1990年 | 107篇 |
1989年 | 101篇 |
1988年 | 86篇 |
1987年 | 59篇 |
1986年 | 77篇 |
1985年 | 86篇 |
1984年 | 79篇 |
1983年 | 48篇 |
1982年 | 45篇 |
1981年 | 48篇 |
1980年 | 23篇 |
1979年 | 13篇 |
1978年 | 15篇 |
1977年 | 5篇 |
1976年 | 8篇 |
1971年 | 4篇 |
排序方式: 共有6832条查询结果,搜索用时 15 毫秒
1.
2.
Numerous data suggested that the pharmacological and biochemical properties of 5-hydroxytryptamine1A (5-HT1A) receptors exhibit some regional differences in the CNS, notably within the raphe nuclei compared with various forebrain areas (such as the hippocampus). This possibility has been further investigated in the dorsal raphe nucleus and two areas within the hippocampus, the dentate gyrus and the CA1 area, using the quantitative autoradiographic technique. The potencies of 5'-guanylylimidodiphosphate to inhibit the specific binding of 125I-Bolton-Hunter-8-methoxy-2-(N-propyl-N-propylamino)tetralin (125I-BH-8-MeO-N-PAT) to 5-HT1A sites and of N-ethylmaleimide to block these sites irreversibly were identical in the dorsal raphe nucleus and the hippocampal areas in rat brain sections. In contrast, slight but significant differences were noted in the pH dependence and pharmacological properties of 5-HT1A sites labeled by 125I-BH-8-MeO-N-PAT in these three regions. Similarly, heat denaturation experiments and tissue exposure to either phospholipase A2 or the alkylating agent 8-methoxy-2-(N-2'-chloropropyl,N-propyl)aminotetraline revealed regional differences in the properties of 5-HT1A sites. However, in most cases, the observed variations were of greater amplitude between the CA1 area and the dentate gyrus, where 5-HT1A sites are located postsynaptically, than between any one of these areas and the dorsal raphe nucleus where they act as (presynaptic) somatodendritic autoreceptors. These data further support that subtypes of 5-HT1A receptors probably exist in the rat brain, but this heterogeneity seems unrelated to the pre- or post-synaptic location of these receptors. 相似文献
3.
《Developmental cell》2020,52(6):714-730.e5
- Download : Download high-res image (188KB)
- Download : Download full-size image
4.
Mandy L. Roberts-Crowley Tora Mitra-Ganguli Liwang Liu Ann R. Rittenhouse 《Cell calcium》2009,45(6):589-601
Great skepticism has surrounded the question of whether modulation of voltage-gated Ca2+ channels (VGCCs) by the polyunsaturated free fatty acid arachidonic acid (AA) has any physiological basis. Here we synthesize findings from studies of both native and recombinant channels where micromolar concentrations of AA consistently inhibit both native and recombinant activity by stabilizing VGCCs in one or more closed states. Structural requirements for these inhibitory actions include a chain length of at least 18 carbons and multiple double bonds located near the fatty acid's carboxy terminus. Acting at a second site, AA increases the rate of VGCC activation kinetics, and in CaV2.2 channels, increases current amplitude. We present evidence that phosphatidylinositol 4,5-bisphosphate (PIP2), a palmitoylated accessory subunit (β2a) of VGCCs and AA appear to have overlapping sites of action giving rise to complex channel behavior. Their actions converge in a physiologically relevant manner during muscarinic modulation of VGCCs. We speculate that M1 muscarinic receptors may stimulate multiple lipases to break down the PIP2 associated with VGCCs and leave PIP2's freed fatty acid tails bound to the channels to confer modulation. This unexpectedly simple scheme gives rise to unanticipated predictions and redirects thinking about lipid regulation of VGCCs. 相似文献
5.
Bone morphogenetic protein 2 (BMP-2) has been known for decades as a strong osteoinductive factor and for clinical applications is combined solely with collagen as carrier material. The growing concerns regarding side effects and the importance of BMP-2 in several developmental and physiological processes have raised the need to improve the design of materials by controlling BMP-2 presentation. Inspired by the natural cell environment, new material surfaces have been engineered and tailored to provide both physical and chemical cues that regulate BMP-2 activity. Here we describe surfaces designed to present BMP-2 to cells in a spatially and temporally controlled manner. This is achieved by trapping BMP-2 using physicochemical interactions, either covalently grafted or combined with other extracellular matrix components. In the near future, we anticipate that material science and biology will integrate and further develop tools for in vitro studies and potentially bring some of them toward in vivo applications. 相似文献
6.
7.
《Neuron》2020,105(6):1062-1076.e6
8.
Bone Cell-autonomous Contribution of Type 2 Cannabinoid Receptor to Breast Cancer-induced Osteolysis
Antonia Sophocleous Silvia Marino John G. Logan Patrick Mollat Stuart H. Ralston Aymen I. Idris 《The Journal of biological chemistry》2015,290(36):22049-22060
The cannabinoid type 2 receptor (CB2) has previously been implicated as a regulator of tumor growth, bone remodeling, and bone pain. However, very little is known about the role of the skeletal CB2 receptor in the regulation of osteoblasts and osteoclasts changes associated with breast cancer. Here we found that the CB2-selective agonists HU308 and JWH133 reduced the viability of a variety of parental and bone-tropic human and mouse breast cancer cells at high micromolar concentrations. Under conditions in which these ligands are used at the nanomolar range, HU308 and JWH133 enhanced human and mouse breast cancer cell-induced osteoclastogenesis and exacerbated osteolysis, and these effects were attenuated in cultures obtained from CB2-deficient mice or in the presence of a CB2 receptor blocker. HU308 and JWH133 had no effects on osteoblast growth or differentiation in the presence of conditioned medium from breast cancer cells, but under these circumstances both agents enhanced parathyroid hormone-induced osteoblast differentiation and the ability to support osteoclast formation. Mechanistic studies in osteoclast precursors and osteoblasts showed that JWH133 and HU308 induced PI3K/AKT activity in a CB2-dependent manner, and these effects were enhanced in the presence of osteolytic and osteoblastic factors such as RANKL (receptor activator of NFκB ligand) and parathyroid hormone. When combined with published work, these findings suggest that breast cancer and bone cells exhibit differential responses to treatment with CB2 ligands depending upon cell type and concentration used. We, therefore, conclude that both CB2-selective activation and antagonism have potential efficacy in cancer-associated bone disease, but further studies are warranted and ongoing. 相似文献
9.
10.