全文获取类型
收费全文 | 78209篇 |
免费 | 3205篇 |
国内免费 | 7173篇 |
专业分类
88587篇 |
出版年
2023年 | 699篇 |
2022年 | 1135篇 |
2021年 | 1415篇 |
2020年 | 1502篇 |
2019年 | 2791篇 |
2018年 | 1806篇 |
2017年 | 1492篇 |
2016年 | 1893篇 |
2015年 | 3020篇 |
2014年 | 3971篇 |
2013年 | 5394篇 |
2012年 | 3407篇 |
2011年 | 4739篇 |
2010年 | 3456篇 |
2009年 | 3492篇 |
2008年 | 3718篇 |
2007年 | 3961篇 |
2006年 | 3590篇 |
2005年 | 3128篇 |
2004年 | 2605篇 |
2003年 | 2292篇 |
2002年 | 2005篇 |
2001年 | 1623篇 |
2000年 | 1431篇 |
1999年 | 1428篇 |
1998年 | 1317篇 |
1997年 | 1145篇 |
1996年 | 1028篇 |
1995年 | 1254篇 |
1994年 | 1169篇 |
1993年 | 1111篇 |
1992年 | 1137篇 |
1991年 | 944篇 |
1990年 | 871篇 |
1989年 | 823篇 |
1988年 | 825篇 |
1987年 | 810篇 |
1986年 | 528篇 |
1985年 | 954篇 |
1984年 | 1339篇 |
1983年 | 962篇 |
1982年 | 1306篇 |
1981年 | 921篇 |
1980年 | 929篇 |
1979年 | 879篇 |
1978年 | 507篇 |
1977年 | 417篇 |
1976年 | 338篇 |
1975年 | 263篇 |
1973年 | 262篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
72.
Hisao Tsukamoto Yoshihiro Kubo David L. Farrens Mitsumasa Koyanagi Akihisa Terakita Yuji Furutani 《The Journal of biological chemistry》2015,290(45):27176-27187
Melanopsins play a key role in non-visual photoreception in mammals. Their close phylogenetic relationship to the photopigments in invertebrate visual cells suggests they have evolved to acquire molecular characteristics that are more suited for their non-visual functions. Here we set out to identify such characteristics by comparing the molecular properties of mammalian melanopsin to those of invertebrate melanopsin and visual pigment. Our data show that the Schiff base linking the chromophore retinal to the protein is more susceptive to spontaneous cleavage in mammalian melanopsins. We also find this stability is highly diversified between mammalian species, being particularly unstable for human melanopsin. Through mutagenesis analyses, we find that this diversified stability is mainly due to parallel amino acid substitutions in extracellular regions. We propose that the different stability of the retinal attachment in melanopsins may contribute to functional tuning of non-visual photoreception in mammals. 相似文献
73.
CHRISTOPHE GONINDARD CATHERINE GOIGOUX ETIENNE HOLLANDE LUCIEN DUSSOURD D'HINTERLAND 《Pigment cell & melanoma research》1996,9(3):148-153
The injection of α-MSH or of one of its analogues ([Nle4-D.Phe7] α-MSH4–10) reduced, in vivo, the release of two cytokines (IL-1α and TNFα) involved in inflammation. The inflammatory state was induced in BALB/c mice by intraperitoneal injection of a sublethal dose of lipopolysaccharides (LPS). The assay of these cytokines by ELISA showed a reduction of 20% with α-MSH and between 30 and 60% with the α-MSH analogue. The α-MSH or the analogue was administered in one of two ways: intravenously or subcutaneously. The most efficient method seemed to be the subcutaneous one because it improved the activity 10,000 times more than the intravenous method. Moreover, the analogue induced a regression of mortality in the animals treated by the intravenous method. Our results show that α-MSH and one of its analogues inhibit IL-1α and TNFα, and can be used as anti-inflammatory molecules. 相似文献
74.
We describe a new tracer method to measure unidirectional fluxes of Li+, despite the lack of any utilizable radioisotope of lithium. This method uses the purified stable isotopes, 6Li and 7Li, detected with an ion-probe microanalyser. The accuracy is comparable to that obtained for other ions (e.g., Na+) with radiotracers.The method has been applied to frog skin with both faces bathed in a 20% lithium/80% sodium medium. Sodium and lithium unidirectional fluxes have been measured simultaneously. The results are consistent with lithium being actively pumped, the outflux of lithium being, however, much larger than that of sodium. 相似文献
75.
Karlheinz Grillitsch Pablo Tarazona Lisa Klug Tamara Wriessnegger Günther Zellnig Erich Leitner Ivo Feussner Günther Daum 《生物化学与生物物理学报:生物膜》2014
Despite similarities of cellular membranes in all eukaryotes, every compartment displays characteristic and often unique features which are important for the functions of the specific organelles. In the present study, we biochemically characterized the plasma membrane of the methylotrophic yeast Pichia pastoris with emphasis on the lipids which form the matrix of this compartment. Prerequisite for this effort was the design of a standardized and reliable isolation protocol of the plasma membrane at high purity. Analysis of isolated plasma membrane samples from P. pastoris revealed an increase of phosphatidylserine and a decrease of phosphatidylcholine compared to bulk membranes. The amount of saturated fatty acids in the plasma membrane was higher than in total cell extracts. Ergosterol, the final product of the yeast sterol biosynthetic pathway, was found to be enriched in plasma membrane fractions, although markedly lower than in Saccharomyces cerevisiae. A further characteristic feature of the plasma membrane from P. pastoris was the enrichment of inositol phosphorylceramides over neutral sphingolipids, which accumulated in internal membranes. The detailed analysis of the P. pastoris plasma membrane is discussed in the light of cell biological features of this microorganism especially as a microbial cell factory for heterologous protein production. 相似文献
76.
Summary Two previously identified forms of macrophage were investigated in primary cultures of cerebral cortical cells. Dynamic features were revealed through time-lapse video recording and aspects of macrophage function were assessed. The two cell forms were shown to be different pre-mitotic stages of a single cell type. The cell cycle for these cells involved an initial large, flat, quiescent cell which retracted to yield a slightly rounded form with numerous processes. This latter form lost processes and developed profuse filopodia as it became very rounded just prior to division; both resulting daughter cells then regained the initial large flat appearance. These cells possessed several properties of macrophages, including phagocytosis, nucleoside diphosphatase enzyme, and CR3 receptors. These properties were transient, expressed just before and after mitosis, but subsequently down-regulated in the flat daughter cells. Because of this feature, it was difficult to determine the exact size of this cell population; however, the observed rate of proliferation suggests it may be substantial. It is suggested that these cells correspond to non-microglial macrophages of brain tissue and, because of their significant down-regulation, they may be difficult to detect. This may be important in studies of brain accessory immune cells in tissue culture. 相似文献
77.
Isabelle Matricon 《Cell and tissue research》1973,136(4):569-578
Résumé L'épithélium pharyngien d'Alcyonidium polyoum possède des cellules pourvues d'une très grande vacuole. L'incompressibilité du liquide vacuolaire permet un élargissement brusque de l'organe lors de la contraction du manchon musculaire strié qui enserre cette vacuole. Les fibres musculaires sont insérées sur le plasmalemme apical par des filaments unitifs. Le point d'attache est relié à la lame amorphe du cell-coat qui entoure les microvillosités par des fibrilles, réalisant probablement une liaison mécamique plus efficace. Le reticulum sarcoplasmique porte des ribosomes. Le cytoplasme apical renferme des vésicules de diverses catégories.
Some ultrastructural data about a myoepithelium: The pharynx of a bryozoan
Summary Pharyngeal cells of Alcyonidium polyoum (Bryozoa) are provided with very large vacuoles. Each vacuole is enveloped by a thin layer of striated muscle, whose contraction enlarges the organ. Filaments join the muscular elements to the apical plasmalemma. This point of muscular insertion is connected by fibrils with the amorphic lamina of cell-coat which surrounds the microvilli. Ribosomes are often found on dyads. Various vesicles are located in the apical cytoplasm.相似文献
78.
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
79.
Wolfram Nagel 《生物化学与生物物理学报:生物膜》1980,599(2):736-740
Inhibition by ouabain of rheogenic Na+ transport across the basolateral membranes of frog skin is found to be manifest within 3–4 min. This rate of pump inhibition is not different from the rate of diffusion through extracellular tissue layers between the serosal bath and the actual site of action, i.e., the epithelial cell layers. It is concluded that the well-known slow time course of decrease in transepithelial current flow is due ionic redistribution and conductance changes of the epithelial membranes secondary to pump inhibition. 相似文献