全文获取类型
收费全文 | 3689篇 |
免费 | 233篇 |
国内免费 | 109篇 |
专业分类
4031篇 |
出版年
2024年 | 7篇 |
2023年 | 49篇 |
2022年 | 42篇 |
2021年 | 92篇 |
2020年 | 99篇 |
2019年 | 99篇 |
2018年 | 118篇 |
2017年 | 69篇 |
2016年 | 94篇 |
2015年 | 101篇 |
2014年 | 185篇 |
2013年 | 380篇 |
2012年 | 124篇 |
2011年 | 175篇 |
2010年 | 134篇 |
2009年 | 182篇 |
2008年 | 188篇 |
2007年 | 208篇 |
2006年 | 178篇 |
2005年 | 151篇 |
2004年 | 158篇 |
2003年 | 158篇 |
2002年 | 116篇 |
2001年 | 107篇 |
2000年 | 105篇 |
1999年 | 106篇 |
1998年 | 89篇 |
1997年 | 64篇 |
1996年 | 64篇 |
1995年 | 66篇 |
1994年 | 57篇 |
1993年 | 37篇 |
1992年 | 23篇 |
1991年 | 19篇 |
1990年 | 18篇 |
1989年 | 19篇 |
1988年 | 19篇 |
1987年 | 13篇 |
1986年 | 13篇 |
1985年 | 23篇 |
1984年 | 19篇 |
1983年 | 7篇 |
1982年 | 18篇 |
1981年 | 14篇 |
1980年 | 4篇 |
1979年 | 10篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有4031条查询结果,搜索用时 15 毫秒
141.
Liwang Liu Laurent Plawinski Marie‐Christine Durrieu Bertrand Audoin 《Journal of biophotonics》2019,12(8)
Advances in microscopy with new visualization possibilities often bring dramatic progress to our understanding of the intriguing cellular machinery. Picosecond optoacoustic micro‐spectroscopy is an optical technique based on ultrafast pump‐probe generation and detection of hypersound on time durations of picoseconds and length scales of nanometers. It is experiencing a renaissance as a versatile imaging tool for cell biology research after a plethora of applications in solid‐state physics. In this emerging context, this work reports on a dual‐probe architecture to carry out real‐time parallel detection of the hypersound propagation inside a cell that is cultured on a metallic substrate, and of the hypersound reflection at the metal/cell adhesion interface. Using this optoacoustic modality, several biophysical properties of the cell can be measured in a noncontact and label‐free manner. Its abilities are demonstrated with the multiple imaging of a mitotic macrophage‐like cell in a single run experiment. 相似文献
142.
Kuldeepsinh Rana Jane L. Liesveld Michael R. King 《Biotechnology and bioengineering》2009,102(6):1692-1702
The survival rate for patients with metastases versus localized cancer is dramatically reduced, with most deaths being associated with the formation of secondary tumors. Circulating cancer cells interact with the endothelial lining of the vasculature via a series of adhesive interactions that facilitate tethering and firm adhesion of cancer cells in the initial steps of metastasis. TNF‐related apoptosis‐inducing ligand (TRAIL) holds promise as a tumor‐specific cancer therapeutic, by inducing a death signal by apoptosis via the caspase pathway. In this study, we exploit this phenomenon to deliver a receptor‐mediated apoptosis signal to leukemic cells adhesively rolling along a TRAIL and selectin‐bearing surface. Results show that cancer cells exhibit selectin‐mediated rolling in capillary flow chambers, and that the rolling velocities can be controlled by varying the selectin and selectin surface density and the applied shear stress. It was determined that a 1 h rolling exposure to a functionalized TRAIL and E‐selectin surface was sufficient to kill 30% of captured cells compared to static conditions in which 4 h exposure was necessary to kill 30% of the cells. Thus, we conclude that rolling delivery is more effective than static exposure to a TRAIL immobilized surface. We have also verified that there is no significant effect of TRAIL on hematopoietic stem cells and other normal blood cells. This represents the first demonstration of a novel biomimetic method to capture metastatic cells from circulation and deliver an apoptotic signal. Biotechnol. Bioeng. 2009;102: 1692–1702. © 2008 Wiley Periodicals, Inc. 相似文献
143.
144.
Abstract: The L1- and F11-like axonal glycoproteins, implicated in neurite outgrowth and fasciculation, are members of the Ig superfamily comprising multiple fibronectin type III-like domains. Their Ig-like and fibronectin type III-related domains are likely to be composed of seven β-strands arranged in two opposing β-sheets of highly similar topology. Whereas the F11-like molecules lack a transmembrane sequence and are anchored in the plasma membrane by a glycosylphosphatidylinositol, the L1 -like molecules comprise cytoplasmic domains with highly conserved sequence motifs. Most of the latter proteins occur in different isoforms generated by alternative pre-mRNA splicing, which has not been documented for molecules of the F11 subgroup. L1 -like proteins undergo heterophils as well as homophilic interactions, whereas only the former mode of binding was observed for F11 -like proteins. Evidence is accumulating that these Ig superfamily molecules with fibronectin type III-like domains are interacting in a complex manner with each other and molecules of the extracellular matrix. Investigations assigning structure to function reveal that their individual extracellular domains serve distinct binding activities. Recent studies also suggest that L1 and NCAM are implicated in the transduction of transmembrane signals. 相似文献
145.
Yu. A. Nikolaev 《Microbiology》2000,69(3):291-295
The effects of distant interactions (LRI) and culture air on the adhesion ofPseudomonas fluorescens cells were studied. OneP. fluorescens culture was found to diminish the adhesion of cells of another, glassscreened,P. fluorescens culture by 30% (in the absence o air exchange between cultures). This effect was interpreted to be due to penetrating LRI.
Under the combined action ofLRI and culture air (the latter alone reduced cell adhesion by only several percent), the amount of unattached cells increased
2-to 30-fold (on the average, by a factor of nine). Such a great reduction of cell adhesion indicated the synergistic action
ofLRI and culture air. 相似文献
146.
Merel B. Soons 《应用植被学》2006,9(2):271-278
Questions: For wetland plants, dispersal by wind is often overlooked because dispersal by water is generally assumed to be the key dispersal process. This literature review addresses the role of seed dispersal by wind in wetlands. Why is wind dispersal relevant in wetlands? Which seeds are dispersed by wind and how far? And how can our understanding of wind dispersal be applied to wetland conservation and restoration? Methods: Literature review. Results and conclusions: Wind is a widely available seed dispersal vector in wetlands and can transport many seeds over long distances. Unlike water, wind can transport seeds in all directions and is therefore important for dispersal to upstream wetlands and to wetlands not connected by surface water flows. Wind dispersal transports seeds to a wider range of sites than water, and therefore reaches more sites but with lower seed densities. Many wetland plant species have adaptations to facilitate wind dispersal. Dispersal distances increase with decreasing falling velocity of seeds, increasing seed release height and selective release mechanisms. Depending on the adaptations, seeds may be dispersed by wind over many km or only a few m. The frequency of long‐distance wind dispersal events depends on these adaptations, the number of produced seeds, the structure of the surrounding vegetation, and the frequency of occurrence of suitable weather conditions. Humans reduce the frequency of successful long‐distance wind dispersal events in wetlands through wetland loss and fragmentation (which reduce the number and quality of seeds) and eutrophication (which changes the structure of the vegetation so that seed release into the wind flow becomes more difficult). This is yet another reason to focus on wetland conservation and restoration measures at increased population sizes, prevention of eutrophication, and the restoration of sites at short distances from seed sources. 相似文献
147.
Using single-molecule force spectroscopy to probe ICAM-1 interactions with recombinant αLβ2 immobilized on microspheres and β2 integrin on neutrophils, we quantified an impressive hierarchy of long-lived, high-strength states of the integrin bond, which start from basal levels with integrin activation in solutions of divalent cations and shift dramatically upward to hyperactivated states with cell signaling in leukocytes. Taking advantage of very rare events, we used repeated measurements of bond lifetimes under steady ramps of force to achieve a direct assay for the off-rates of ICAM-1 from β2 integrin in each experiment. Of fundamental importance, the assay for off-rates does not depend on how the force is applied over time, and remains valid when the rates of dissociation change with different levels of force. In this first article, we present results from tests of a monovalent ICAM-1 probe against immobilized αLβ2 in environments of divalent cations (Ca2+, Mg2+, and Mn2+) and demonstrate in detail the method for assay of off-rates. When extrapolated to zero force, the force-free values for the off-rates are found to be consistent with published solution-based assays of soluble ICAM-1 dissociation from immobilized LFA-1, i.e., ∼10−2/s in Mg2+ or Mn2+ and ∼1/s in Ca2+. At the same time, as expected for adhesive function, we find that the β2 integrin bonds activated in Mn2+ or Mg2+ possess significant and persistent mechanical strength (e.g., >20 pN for >1 s) even when subjected to slow force ramps (<10 pN/s). As discussed in our companion article, using the same assay, we find that although the rates of dissociation for diICAM-1fc bonds to LFA-1 on neutrophils in Mn2+ are similar to those for mICAM-1 bonds to recombinant αLβ2 on microspheres, they appear to represent a dimeric attachment to a pair of tightly clustered integrin heterodimers. The mechanical strengths and lifetimes of the dimeric interactions increase dramatically when the neutrophils are stimulated by the chemokine IL-8 or are bound with an allosterically activating (anti-CD18) monoclonal antibody, demonstrating the major impact of cell signaling on LFA-1. 相似文献
148.
Comparative analysis of vascular endothelial cell activation by TNF-α and LPS in humans and baboons 总被引:7,自引:0,他引:7
As an Old World nonhuman primate, baboons have been extensively used for research on dyslipidemia and atherogenesis. With
increasing knowledge about the endothelium's role in the initiation and progression of atherosclerosis, the value of the baboon
model can be increased by developing it for research on the role of dysfunctional endothelium in atherogenesis. Toward that
goal, we have established and validated methods of isolating and culturing baboon femoral artery endothelial cells (BFAECs)
and compared baboon endothelial cellular characteristics with those of humans. Our results indicated that baboon and human
endothelial cells share similar growth and culture behaviors. As was the case for human endothelial cells, BFAECs responded
to tumor necrosis factor (TNF)-α stimulation with increased expression of adhesion molecules (maximum increase for intracellular
adhesion molecule (ICAM): 1.76±0.26-fold; vascular cell adhesion molecule (VCAM): 1.65±0.25-fold; E-selectin: 2.86±0.57-fold).
However, BFAECs were hyporesponsive to lipopolysaccharide (LPS) (range, 0.25–20 μg/mL) in adhesion molecule expression, whereas
1 μg/mL LPS induced 2.14- to 3.71-fold increases in human endothelial cells. The differential responses to LPS were not related
to TLR-2 and toll-like receptor (TLR)-4 expression on the cell surface. And baboon microvascular endothelial cells had similar
features as BFAECs. We observed constitutive expression of interleukin (IL)-6, IL-8, granulocyte macrophage colony-stimulating
factor (GM-CSF), and monocyte chemoattractant protein (MCP)-1 in both human and baboon endothelial cells, and these cytokines
were further induced by TNF-α and LPS. We also demonstrated that the responses to TNF-α or LPS varied among baboons maintained
under the same dietary and environmental conditions, suggesting that response may be controlled by genetic factors. 相似文献
149.
The oral streptococci Streptococcus sanguinis, Streptococcus gordonii and Streptococcus oralis are common aetiological agents of infective endocarditis, and their ability to adhere to and induce the aggregation of platelets is thought to be a virulence trait. The platelet glycoprotein GPIbalpha has been implicated as the adhesion receptor for S. sanguinis and S. gordonii, but it is not known if this is the case for S. oralis and other species. The aim of this study was to determine the GPIbalpha-interactive capability of a range of oral streptococci and to determine the relationship between this capability and their ability to interact with the salivary constituents that they would encounter in their normal habitat. All platelet-adhesive S. sanguinis strains and most S. gordonii strains adhered in a GPIbalpha-dependent manner, but strains of S. oralis, Streptococcus cristatus, Streptococcus parasanguinis and Streptococcus mitis had no direct affinity for platelets. Those strains that were able to bind GPIbalpha also bound to the low-molecular-weight submandibular salivary mucin, MG2, and this interaction was sialic acid-dependent. The data suggest that S. sanguinis and S. gordonii may be efficient colonizers of platelet vegetations because of their adaptation to recognize sialylated salivary mucins. In contrast, S. oralis does not interact with platelets and so is likely to colonize vegetations through an as yet unidentified mechanism. 相似文献
150.
Doxazosin inhibits human vascular endothelial cell adhesion, migration, and invasion 总被引:3,自引:0,他引:3
The quinazoline-derived alpha1-adrenoceptor antagonists, doxazosin and terazosin have been recently shown to induce an anoikis effect in human prostate cancer cells and to suppress prostate tumor vascularity in clinical specimens [Keledjian and Kyprianou, 2003]. This study sought to examine the ability of doxazosin to affect the growth of human vascular endothelial cells and to modulate vascular endothelial growth factor (VEGF)-mediated angiogenesis. Human umbilical vein endothelial cells (HUVECs) were used as an in vitro model to determine the effect of doxazosin on cell growth, apoptosis, adhesion, migration, and angiogenic response of endothelial cells. The effect of doxazosin on cell viability and apoptosis induction of human endothelial cells, was evaluated on the basis of trypan blue and Hoechst 33342 staining, respectively. Doxazosin antagonized the VEGF-mediated angiogenic response of HUVEC cells, by abrogating cell adhesion to fibronectin and collagen-coated surfaces and inhibiting cell migration, via a potential downregulation of VEGF expression. Furthermore there was a significant suppression of in vitro angiogenesis by doxazosin on the basis of VEGF-mediated endothelial tube formation (P < 0.01). Fibroblast growth factor-2 (FGF-2) significantly enhanced HUVEC cell tube formation (P < 0.01) and this effect was suppressed by doxazosin. These findings provide new insight into the ability of doxazosin to suppress the growth and angiogenic response of human endothelial cells by interfering with VEGF and FGF-2 action. This evidence may have potential therapeutic significance in using this quinazoline-based compound as an antiangiogenic agent for the treatment of advanced prostate cancer. 相似文献