全文获取类型
收费全文 | 2884篇 |
免费 | 266篇 |
国内免费 | 138篇 |
专业分类
3288篇 |
出版年
2023年 | 25篇 |
2022年 | 70篇 |
2021年 | 82篇 |
2020年 | 68篇 |
2019年 | 76篇 |
2018年 | 99篇 |
2017年 | 81篇 |
2016年 | 101篇 |
2015年 | 109篇 |
2014年 | 119篇 |
2013年 | 158篇 |
2012年 | 175篇 |
2011年 | 189篇 |
2010年 | 133篇 |
2009年 | 102篇 |
2008年 | 144篇 |
2007年 | 129篇 |
2006年 | 117篇 |
2005年 | 96篇 |
2004年 | 87篇 |
2003年 | 80篇 |
2002年 | 92篇 |
2001年 | 63篇 |
2000年 | 62篇 |
1999年 | 51篇 |
1998年 | 32篇 |
1997年 | 19篇 |
1996年 | 15篇 |
1994年 | 14篇 |
1992年 | 48篇 |
1991年 | 43篇 |
1990年 | 39篇 |
1989年 | 33篇 |
1988年 | 28篇 |
1987年 | 34篇 |
1986年 | 32篇 |
1985年 | 29篇 |
1984年 | 25篇 |
1983年 | 24篇 |
1982年 | 20篇 |
1981年 | 33篇 |
1980年 | 25篇 |
1979年 | 20篇 |
1978年 | 34篇 |
1977年 | 22篇 |
1976年 | 18篇 |
1975年 | 18篇 |
1974年 | 14篇 |
1973年 | 19篇 |
1969年 | 14篇 |
排序方式: 共有3288条查询结果,搜索用时 15 毫秒
981.
982.
Bacteria can exist within biofilms that are attached to the solid matrix of a porous medium. Under certain conditions, the biomass can fully occupy the pore space leading to reduced hydraulic conductivity and mass transport. Here, by treating biofilm as a growing, high-viscosity phase, a novel macroscopic approach to model biofilm spatial expansion and its corresponding effects on porous medium hydraulic properties is presented. The separate yet coupled flow of the water and biofilm phases is handled by using relative permeability curves that allow for biofilm movement within the porous medium and bioclogging effects. Fluid flow is governed by Darcy's law and component transport is set by the convection-diffusion equation reaction terms for each component. Here, the system of governing equations is solved by using a commercial multiphase flow reservoir simulator, which is used to validate the model against published laboratory experiments. A comparison of the model and experimental observations reveal that the model provides a reasonable means to predict biomass development in the porous medium. The results reveal that coupled flow of water and movement of biofilm, as described by relative permeability curves, is complex and has a large impact on the development of biomass and consequent bioclogging in the porous medium. 相似文献
983.
Reichelt M Wang L Sommer M Perrino J Nour AM Sen N Baiker A Zerboni L Arvin AM 《PLoS pathogens》2011,7(2):e1001266
The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs, as shown in cells infected in vitro, but information about the fate of PML-NBs and their functions in herpesvirus infected cells in vivo is limited. Varicella-zoster virus (VZV) is an alphaherpesvirus with tropism for skin, lymphocytes and sensory ganglia, where it establishes latency. Here, we identify large PML-NBs that sequester newly assembled nucleocapsids (NC) in neurons and satellite cells of human dorsal root ganglia (DRG) and skin cells infected with VZV in vivo. Quantitative immuno-electron microscopy revealed that these distinctive nuclear bodies consisted of PML fibers forming spherical cages that enclosed mature and immature VZV NCs. Of six PML isoforms, only PML IV promoted the sequestration of NCs. PML IV significantly inhibited viral infection and interacted with the ORF23 capsid surface protein, which was identified as a target for PML-mediated NC sequestration. The unique PML IV C-terminal domain was required for both capsid entrapment and antiviral activity. Similar large PML-NBs, termed clastosomes, sequester aberrant polyglutamine (polyQ) proteins, such as Huntingtin (Htt), in several neurodegenerative disorders. We found that PML IV cages co-sequester HttQ72 and ORF23 protein in VZV infected cells. Our data show that PML cages contribute to the intrinsic antiviral defense by sensing and entrapping VZV nucleocapsids, thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The efficient sequestration of virion capsids in PML cages appears to be the outcome of a basic cytoprotective function of this distinctive category of PML-NBs in sensing and safely containing nuclear aggregates of aberrant proteins. 相似文献
984.
985.
Zhang Q Cigan AD Marrero L Lopreore C Liu S Ge D Savoie FH You Z 《Genesis (New York, N.Y. : 2000)》2011,49(2):75-82
The doublecortin (Dcx) gene encodes a microtubule-binding protein that was originally found in immature neurons. In this study, we used two mouse strains that express reporter genes (LacZ and enhanced green fluorescence protein, respectively) driven by the endogenous Dcx promoter. We found that Dcx was expressed in the mesenchymal cells in the mouse embryonic limb buds. A population of the mesenchymal cells continued Dcx expression after they differentiated into joint interzone cells and then articular chondrocytes. In contrast, the endochondral chondrocytes lost Dcx expression when the mesenchymal cells differentiated into endochondral chondrocytes. These data support a concept that the articular and endochondral chondrocytes originate from the same mesenchymal cells that express Dcx. In contrast to the notion that articular chondrocytes are derived from de-differentiated endochondral chondrocytes, our findings demonstrate that the lineages of articular and endochondral chondrocytes bifurcate at the stage of endochondral chondrogenesis. 相似文献
986.
Sivapathasekaran C Mukherjee S Sen R Bhattacharya B Samanta R 《Bioprocess and biosystems engineering》2011,34(3):339-346
The extracellular biosurfactant product secreted by a marine bacterium was concentrated and purified directly from the fermentation broth in a single step by ultrafiltration (UF) employing YM 30 kDa (UF-I) and Omega 10 kDa (UF-II) polyethersulfone membranes. The optimum operating pressure required for both membranes, UF-I and UF-II, were found to be 30 and 35 psi, respectively. The biosurfactant from the fermentation broth was recovered in higher amounts using UF-II (89%) than using UF-I (73%). An analysis of the critical micelle concentrations (CMC) of the recovered lipopeptides showed a lower CMC value of 15 mg L?1 for the UF-II product, indicating higher degree of purity (83%) when compared to that of the UF-I product (78%). The ultrafiltered products were characterized using Fourier transformed infrared spectroscopy and matrix-assisted laser desorption ionization time of flight mass spectral analysis, which demonstrated the presence of two families of lipopeptides. 相似文献
987.
Ellora Sen Anirban Basu Lisa B Willing Tracy F Uliasz Jaimie L Myrkalo Susan J Vannucci Sandra J Hewett Steven W Levison 《ASN neuro》2011,3(3)
Hypoxic preconditioning reprogrammes the brain''s response to subsequent H/I (hypoxia–ischaemia) injury by enhancing neuroprotective mechanisms. Given that astrocytes normally support neuronal survival and function, the purpose of the present study was to test the hypothesis that a hypoxic preconditioning stimulus would activate an adaptive astrocytic response. We analysed several functional parameters 24 h after exposing rat pups to 3 h of systemic hypoxia (8% O2). Hypoxia increased neocortical astrocyte maturation as evidenced by the loss of GFAP (glial fibrillary acidic protein)-positive cells with radial morphologies and the acquisition of multipolar GFAP-positive cells. Interestingly, many of these astrocytes had nuclear S100B. Accompanying their differentiation, there was increased expression of GFAP, GS (glutamine synthetase), EAAT-1 (excitatory amino acid transporter-1; also known as GLAST), MCT-1 (monocarboxylate transporter-1) and ceruloplasmin. A subsequent H/I insult did not result in any further astrocyte activation. Some responses were cell autonomous, as levels of GS and MCT-1 increased subsequent to hypoxia in cultured forebrain astrocytes. In contrast, the expression of GFAP, GLAST and ceruloplasmin remained unaltered. Additional experiments utilized astrocytes exposed to exogenous dbcAMP (dibutyryl-cAMP), which mimicked several aspects of the preconditioning response, to determine whether activated astrocytes could protect neurons from subsequent excitotoxic injury. dbcAMP treatment increased GS and glutamate transporter expression and function, and as hypothesized, protected neurons from glutamate excitotoxicity. Taken altogether, these results indicate that a preconditioning stimulus causes the precocious differentiation of astrocytes and increases the acquisition of multiple astrocytic functions that will contribute to the neuroprotection conferred by a sublethal preconditioning stress. 相似文献
988.
Sivakumaran TA Igo RP Kidd JM Itsara A Kopplin LJ Chen W Hagstrom SA Peachey NS Francis PJ Klein ML Chew EY Ramprasad VL Tay WT Mitchell P Seielstad M Stambolian DE Edwards AO Lee KE Leontiev DV Jun G Wang Y Tian L Qiu F Henning AK LaFramboise T Sen P Aarthi M George R Raman R Das MK Vijaya L Kumaramanickavel G Wong TY Swaroop A Abecasis GR Klein R Klein BE Nickerson DA Eichler EE Iyengar SK 《PloS one》2011,6(10):e25598
Complement factor H shows very strong association with Age-related Macular Degeneration (AMD), and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP), CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N = 293) and AMD cases (White N = 4210 Indian = 134; Malay = 140) and controls (White N = 3229; Indian = 117; Malay = 2390) demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH. Regression analysis of seven common haplotypes showed three haplotypes, H1, H6 and H7, as conferring risk for AMD development. Being the most common haplotype H1 confers the greatest risk by increasing the odds of AMD by 2.75-fold (95% CI = [2.51, 3.01]; p = 8.31×10−109); Caucasian (H6) and Indian-specific (H7) recombinant haplotypes increase the odds of AMD by 1.85-fold (p = 3.52×10−9) and by 15.57-fold (P = 0.007), respectively. We identified a 32-kb region downstream of Y402H (rs1061170), shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Further analysis showed that two SNPs within the 32 kb block, rs1329428 and rs203687, optimally explain disease association. rs1329428 resides in 20 kb unique sequence block, but rs203687 resides in a 12 kb block that is 89% similar to a noncoding region contained in ΔCNP148. We conclude that causal variation in this region potentially encompasses both regulatory effects at single markers and copy number. 相似文献
989.
990.