全文获取类型
收费全文 | 3015篇 |
免费 | 258篇 |
国内免费 | 2篇 |
出版年
2024年 | 2篇 |
2023年 | 18篇 |
2022年 | 25篇 |
2021年 | 97篇 |
2020年 | 44篇 |
2019年 | 73篇 |
2018年 | 95篇 |
2017年 | 87篇 |
2016年 | 87篇 |
2015年 | 150篇 |
2014年 | 176篇 |
2013年 | 207篇 |
2012年 | 274篇 |
2011年 | 265篇 |
2010年 | 169篇 |
2009年 | 123篇 |
2008年 | 203篇 |
2007年 | 206篇 |
2006年 | 178篇 |
2005年 | 164篇 |
2004年 | 164篇 |
2003年 | 140篇 |
2002年 | 141篇 |
2001年 | 20篇 |
2000年 | 18篇 |
1999年 | 17篇 |
1998年 | 18篇 |
1997年 | 19篇 |
1996年 | 14篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 9篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1968年 | 2篇 |
1957年 | 1篇 |
1954年 | 1篇 |
1946年 | 1篇 |
排序方式: 共有3275条查询结果,搜索用时 741 毫秒
1.
Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE2 Production
Reginaldo K. Fernandes Tatiana F. Bachiega Daniela R. Rodrigues Marjorie de A. Golim Luciane A. Dias-Melicio Helanderson de A. Balderramas Ramon Kaneno ?ngela M. V. C. Soares 《PloS one》2015,10(3)
Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil, whose etiologic agent is the thermodimorphic fungus of the genus Paracoccidioides, comprising cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii. The mechanisms involved in the initial interaction of the fungus with cells of the innate immune response, as dendritic cells (DCs), deserve to be studied. Prostaglandins (PGs) are eicosanoids that play an important role in modulating functions of immune cells including DCs. Here we found that human immature DCs derived from the differentiation of monocytes cultured with GM-CSF and IL-4 release substantial concentrations of PGE2, which, however, were significantly inhibited after challenge with P. brasiliensis. In vitro blocking of pattern recognition receptors (PRRs) by monoclonal antibodies showed the involvement of mannose receptor (MR) in PGE2 inhibition by the fungus. In addition, phenotyping assays showed that after challenge with the fungus, DCs do not change their phenotype of immature cells to mature ones, as well as do not produce IL-12 p70 or adequate concentrations of TNF-α. Assays using exogenous PGE2 confirmed an association between PGE2 inhibition and failure of cells to phenotypically mature in response to P. brasiliensis. We conclude that a P. brasiliensis evasion mechanism exists associated to a dysregulation on DC maturation. These findings may provide novel information for the understanding of the complex interplay between the host and this fungus. 相似文献
2.
A. S. Radchenko V. E. Borilkevich A. V. Borodin A. I. Zorin A. V. Mirolyubov 《Human physiology》2002,28(1):65-74
Spectral, coherent, and phase analysis within the low-frequency range of ECG records of athletic runners revealed that oscillations of ECG intervals (PQ-, RT-, P–T-, TP, and PP-intervals) were observed during orthostasis. These data were compared with the results of athletic exercise tests performed after the ECG examination. It was shown that the most effective type of adaptive reaction in these tests corresponds to a phase advance of the PQ-interval oscillations relative to the RT-interval oscillations. In the low-frequency range, the phases of the PQ-, RT-, and (P–T)-interval oscillations were ahead of the TP-interval oscillations, whereas the spectral density of the TP interval oscillations was significantly higher than the spectral density of the oscillations of the PC-, RT-, and (P–T)-intervals measured at the same frequency. The least effective type of adaptive reaction was shown to correlate with the phase advance of the TP-interval oscillations relative to the PQ-, RT-, and (P–T)-interval oscillations within the low-frequency range as well as with the lack of low-frequency modulation of the autospectra of the cardiac intervals of interest. 相似文献
3.
Theofilos Poutahidis Sean M. Kearney Tatiana Levkovich Peimin Qi Bernard J. Varian Jessica R. Lakritz Yassin M. Ibrahim Antonis Chatzigiagkos Eric J. Alm Susan E. Erdman 《PloS one》2013,8(10)
Wound healing capability is inextricably linked with diverse aspects of physical fitness ranging from recovery after minor injuries and surgery to diabetes and some types of cancer. Impact of the microbiome upon the mammalian wound healing process is poorly understood. We discover that supplementing the gut microbiome with lactic acid microbes in drinking water accelerates the wound-healing process to occur in half the time required for matched control animals. Further, we find that Lactobacillus reuteri enhances wound-healing properties through up-regulation of the neuropeptide hormone oxytocin, a factor integral in social bonding and reproduction, by a vagus nerve-mediated pathway. Bacteria-triggered oxytocin serves to activate host CD4+Foxp3+CD25+ immune T regulatory cells conveying transplantable wound healing capacity to naive Rag2-deficient animals. This study determined oxytocin to be a novel component of a multi-directional gut microbe-brain-immune axis, with wound-healing capability as a previously unrecognized output of this axis. We also provide experimental evidence to support long-standing medical traditions associating diet, social practices, and the immune system with efficient recovery after injury, sustained good health, and longevity. 相似文献
4.
Tatiana V. Byzova Wes Kim Ronald J. Midura Edward F. Plow 《Experimental cell research》2000,254(2):299
αVβ3, a broadly distributed member of the integrin family of adhesion receptors, has been implicated in a variety of physiological and pathophysiological events, including control of bone density, angiogenesis, apoptosis, tumor growth, and metastasis. Recently, it has been shown that activation of αVβ3, its transition from a low- to a high-affinity/avidity state, influences its recognition of certain ligands. Bone sialoprotein (BSP) is recognized as an important ligand for αVβ3 in processes ranging from bone formation to the homing of metastatic tumor cells. Here, the influence of αVβ3 activation on the adhesion and migration of relevant cells to BSP has been examined. Stimulation of lymphoblastoid, osteoblastoid, and human umbilical vein endothelial cells (HUVEC) with PMA or Mn2+ markedly enhanced αVβ3-dependent adhesion to BSP. αVβ3-mediated migration of HUVEC or osteoblastic cells to BSP was substantially enhanced by stimulation, demonstrating that αVβ3 activation enhances both adhesive and migratory responses. However, adhesion and/or migration of certain tumor cell lines, including M21 melanoma and MDA MB435 and SKBR3 breast carcinoma cell lines, to BSP was constitutively high and was not augmented by αVβ3-activating stimuli. Inhibitors of the intracellular signaling molecules, phosphatidylinositol 3-kinase with wortmannin, hsp90-dependent kinases with geldanamycin, and calpain with calpeptin, but not MAPKK with PD98059, reduced the high spontaneous adhesion and migration of the M21 cells to BSP, consistent with the constitutive activation of the receptor on these tumor cells. These results indicate that the activation state of αVβ3 can regulate cell migration and adhesion to BSP and, by extension, to other ligands of this receptor. The constitutive activation of αVβ3 on neoplastic cells may contribute to tumor growth and metastatic potential. 相似文献
5.
A I Radchenko 《Tsitologiia》1991,33(3):95-100
An electron microscope study of sulfatized glycosaminoglycans (SG) was made for cyst stages of S. muris. The polysaccharides were detected in the submembranous and subwall layers of the sarcocysts, in addition to the ground substance and septae. Moreover SG were discovered in the cyst stages themselves--metrocytes, intermediate cells and merozoites (gamonts). SG were discernible as electron dark spots in vacuoles of the metrocytes. SG shaped as granules were scattered in the cytoplasm of both intermediate cells and merozoites. More granules of SG were seen in the cytoplasm of the merozoites compared to the intermediate cells. Thus, the quantity, localization and structure of SG are seen to follow the process of differentiation in muscle cysts of S. muris. 相似文献
6.
7.
Tatiana I. Gerasimova Yurii V. Ilyin Lev J. Mizrokhi Liliya V. Semjonova Georgii P. Georgiev 《Molecular & general genetics : MGG》1984,193(3):488-492
Summary A family of unstable mutations at the cut locus in Drosophila melanogaster was obtained under the conditions of hybrid dysgenesis (Gerasimova 1981, 1982). The in situ hybridization experiments have shown that, in the original unstable ct
MR2 mutation, the 7B region of the X chromosome (where cut is located) contains a mobile dispersed genetic element, mdg4. All other unstable ct mutations derived from ct
MR2 including visible and lethal alleles and unstable ct
+ reversions, also contain mdg4 in the 7B region. The X chromosomes of the parent strain (wild type) do not contain mdg4 at all. All stable revertants derived from ct
MR2, from other unstable ct mutations, or from ct lethals lost mdg4 from the 7B region. The ct
MR2 X chromosome does not contain P-elements, although a few copies are present in the autosomes. The instability of the ct
MR2./ct
MR2 strain remained at a high level for 50 generations (1.5 years) and then rapidly decreased. A new cross with an MRh12/Cy strain (originally used for dysgenesis induction and containing a number of P-elements) increased the instability to a level exceeding the original one. The data strongly suggest that unstable ct mutations in our system are induced by transpositions of mdg4, possibly activated by P-elements. 相似文献
8.
N I Neshev Iu G Bogdanova E V Radchenko I K Sarycheva 《Izvestiia Akademii nauk SSSR. Seriia biologicheskaia》1989,(2):290-293
The effect of alpha-tocopherol and its synthetic analogue which does not contain an isoprenoid chain, 2,2,5,7,8-pentamethyl-6-hydroxychroman (chromanol), on rat erythrocyte and hemoglobin has been studied. Chromanol, unlike alpha-tocopherol, induces oxidation of hemoglobin into aquomethemoglobin and causes erythrocyte hemolysis. A mechanism of the reaction has been established. It consists of two-electron reduction of haem-associated oxygen molecule. The products formed can cause oxidative membrane damage and subsequent hemolysis. The absence of similar activity of alpha-tocopherol seems to be connected with the inaccessibility of ligand sphere of hemin iron because of the presence of the isoprenoid chain. The oxidative activity of chromanol can explain the absence of E-vitamin activity in this compound. 相似文献
9.
Applications of intrinsic fluorescence measurements in the study of Ca2+-transport ATPases are reviewed. Since the initial reports showing that the fluorescence emission was sensitive to Ca2+ binding, a substantial amount of work has focused on the use of both steady-state and time-resolved fluorescence spectroscopy to investigate structure-function relationships in sarcoplasmic reticulum and plasma membrane Ca2+-ATPases. These studies have revealed ligand-induced conformational changes, as well as provided information on protein-protein, protein-solvent and/or protein-lipid interactions in different functional states of these proteins. The main results of these studies, as well as possible future prospects are discussed. 相似文献
10.
Tatiana L. Hernández-Palma Luis Alberto Rueda-Solano Janne K. Valkonen Bibiana Rojas 《Journal of evolutionary biology》2023,36(7):1040-1049
Deimatic displays, where sudden changes in prey appearance elicit aversive predator reactions, have been suggested to occur in many taxa. These (often only putative) displays frequently involve different components that may also serve antipredator functions via other mechanisms (e.g., mimicry, warning signalling, body inflation). The Colombian four-eyed frog, Pleurodema brachyops, has been suggested to gain protection against predation through putative deimatic displays where they inflate and elevate the posterior part of their body revealing eye-like colour markings. We exposed stationary artificial frogs to wild predators to test whether the two components (eyespot/colour markings, defensive posture) of their putative deimatic display, and their combination, provide protection from predation without the sudden change in appearance. We did not detect any obvious additive effect of defensive posture and eyespots/colour markings on predation risk, but found a marginally significant trend for model frogs in the resting posture to be less attacked when displaying eyespots/colour markings than when they were not, suggesting that the presence of colour markings/eyespots may provide some protection on its own. Additionally, we found that models in a resting posture were overall more frequently attacked on the head than models in a defensive posture, indicating that a defensive posture alone could help redirect predator attacks to non-vital parts of the body. The trends found in our study suggest that the different components of P. brachyops' coloration may serve different functions during a deimatic display, but further research is needed to elucidate the role of each component when accompanied by sudden prey movement. 相似文献