全文获取类型
收费全文 | 59668篇 |
免费 | 4246篇 |
国内免费 | 34篇 |
专业分类
63948篇 |
出版年
2021年 | 613篇 |
2020年 | 357篇 |
2019年 | 415篇 |
2018年 | 577篇 |
2017年 | 540篇 |
2016年 | 952篇 |
2015年 | 1658篇 |
2014年 | 1816篇 |
2013年 | 2833篇 |
2012年 | 2868篇 |
2011年 | 2959篇 |
2010年 | 2013篇 |
2009年 | 2084篇 |
2008年 | 2769篇 |
2007年 | 2771篇 |
2006年 | 2661篇 |
2005年 | 2633篇 |
2004年 | 2517篇 |
2003年 | 2471篇 |
2002年 | 2462篇 |
2001年 | 574篇 |
2000年 | 470篇 |
1999年 | 667篇 |
1998年 | 764篇 |
1997年 | 560篇 |
1996年 | 578篇 |
1995年 | 560篇 |
1994年 | 510篇 |
1993年 | 636篇 |
1992年 | 540篇 |
1991年 | 516篇 |
1990年 | 545篇 |
1989年 | 624篇 |
1988年 | 635篇 |
1987年 | 718篇 |
1986年 | 651篇 |
1985年 | 707篇 |
1984年 | 690篇 |
1983年 | 590篇 |
1982年 | 736篇 |
1981年 | 752篇 |
1980年 | 720篇 |
1979年 | 576篇 |
1978年 | 654篇 |
1977年 | 665篇 |
1976年 | 694篇 |
1975年 | 657篇 |
1974年 | 584篇 |
1973年 | 422篇 |
1972年 | 332篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
951.
Kalyani Nair Milind Gandhi Saif Khalil Karen Chang Yan Michele Marcolongo Kenneth Barbee Wei Sun Dr. 《Biotechnology journal》2009,4(8):1168-1177
Bioprinting is an emerging technology in the field of tissue engineering and regenerative medicine. The process consists of simultaneous deposition of cells, biomaterial and/or growth factors under pressure through a micro-scale nozzle. Cell viability can be controlled by varying the parameters like pressure and nozzle diameter. The process itself can be a very useful tool for evaluating an in vitro cell injury model. It is essential to understand the cell responses to process-induced mechanical disturbances because they alter cell morphology and function. We carried out analysis and quantification of the degree of cell injury induced by bioprinting process. A parametric study with different process parameters was conducted to analyze and quantify cell injury as well as to optimize the parameters for printing viable cells. A phenomenological model was developed correlating the percentage of live, apoptotic and necrotic cells to the process parameters. This study incorporates an analytical formulation to predict the cell viability through the system as a function of the maximum shear stress in the system. The study shows that dispensing pressure has a more significant effect on cell viability than the nozzle diameter. The percentage of live cells is reduced significantly (by 38.75%) when constructs are printed at 40 psi compared to those printed at 5 psi. 相似文献
952.
Richard GH Immink Isabella AN Tonaco Stefan de Folter Anna Shchennikova Aalt DJ van Dijk Jacqueline Busscher-Lange Jan W Borst Gerco C Angenent 《Genome biology》2009,10(2):R24-16
Background
Plant MADS box proteins play important roles in a plethora of developmental processes. In order to regulate specific sets of target genes, MADS box proteins dimerize and are thought to assemble into multimeric complexes. In this study a large-scale yeast three-hybrid screen is utilized to provide insight into the higher-order complex formation capacity of the Arabidopsis MADS box family. SEPALLATA3 (SEP3) has been shown to mediate complex formation and, therefore, special attention is paid to this factor in this study. 相似文献953.
Background
The ability to perform quantitative studies using isotope tracers and metabolic flux analysis (MFA) is critical for detecting pathway bottlenecks and elucidating network regulation in biological systems, especially those that have been engineered to alter their native metabolic capacities. Mathematically, MFA models are traditionally formulated using separate state variables for reaction fluxes and isotopomer abundances. Analysis of isotope labeling experiments using this set of variables results in a non-convex optimization problem that suffers from both implementation complexity and convergence problems.Results
This article addresses the mathematical and computational formulation of 13C MFA models using a new set of variables referred to as fluxomers. These composite variables combine both fluxes and isotopomer abundances, which results in a simply-posed formulation and an improved error model that is insensitive to isotopomer measurement normalization. A powerful fluxomer iterative algorithm (FIA) is developed and applied to solve the MFA optimization problem. For moderate-sized networks, the algorithm is shown to outperform the commonly used 13CFLUX cumomer-based algorithm and the more recently introduced OpenFLUX software that relies upon an elementary metabolite unit (EMU) network decomposition, both in terms of convergence time and output variability.Conclusions
Substantial improvements in convergence time and statistical quality of results can be achieved by applying fluxomer variables and the FIA algorithm to compute best-fit solutions to MFA models. We expect that the fluxomer formulation will provide a more suitable basis for future algorithms that analyze very large scale networks and design optimal isotope labeling experiments. 相似文献954.
David G. Angeler Cristina Trigal Stina Drakare Richard K. Johnson Willem Goedkoop 《Oecologia》2010,164(1):231-241
The complex nature of ecological systems limits the unambiguous determination of mechanisms that drive resilience to natural
disturbance or anthropogenic stress. Using eight-year time series data from boreal lakes with and without bloom formation
of an invasive alga (Gonyostomum semen, Raphidophyceae), we studied resilience of phytoplankton communities in relation to recurring bloom impacts. We first characterized
phytoplankton community dynamics in both lake types using univariate metrics of community structure (evenness, species richness,
biovolume and Simpson diversity). All metrics, except species richness, were substantially altered and showed an inherent
stronger variability in bloom lakes relative to reference lakes. We assessed resilience mechanisms using a multivariate time
series modelling technique. The models captured clear successional dynamics of the phytoplankton communities in all lakes,
whereby different groups of species were substituted sequentially over the ice-free period. The models also identified that
G. semen impacts in bloom lakes were only manifested within a single species group, not across species groups, highlighting the rapid
renewal of the phytoplankton communities upon bloom collapse. These results provide empirical support of the cross-scale resilience
model. Cross-scale resilience could provide an explanation for the paradox that similar species richnesses are seen in bloom-forming
lakes and reference lakes despite the clear difference between the community features of the two different sets of lakes investigated. 相似文献
955.
Amy M. LaFountain Shannon Cawley Steven J. Schwartz Richard O. Prum 《Archives of biochemistry and biophysics》2010,504(1):142-153
Recent advances in the fields of chromatography, mass spectrometry, and chemical analysis have greatly improved the efficiency with which carotenoids can be extracted and analyzed from avian plumage. Prior to these technological developments, Brush (1968) [1] concluded that the burgundy-colored plumage of the male pompadour Cotinga Xipholena punicea is produced by a combination of blue structural color and red carotenoids, including astaxanthin, canthaxanthin, isozeaxanthin, and a fourth unidentified, polar carotenoid. However, X. punicea does not in fact exhibit any structural coloration. This work aims to elucidate the carotenoid pigments of the burgundy color of X. punicea plumage using advanced analytical methodology. Feathers were collected from two burgundy male specimens and from a third aberrant orange-colored specimen. Pigments were extracted using a previously published technique (McGraw et al. (2005) [2]), separated by high-performance liquid chromatography (HPLC), and analyzed by UV/Vis absorption spectroscopy, chemical analysis, mass spectrometry, nuclear magnetic resonance (NMR), and comparison with direct synthetic products. Our investigation revealed the presence of eight ketocarotenoids, including astaxanthin and canthaxanthin as reported previously by Brush (1968) [1]. Six of the ketocarotenoids contained methoxyl groups, which is rare for naturally-occurring carotenoids and a novel finding in birds. Interestingly, the carotenoid composition was the same in both the burgundy and orange feathers, indicating that feather coloration in X. punicea is determined not only by the presence of carotenoids, but also by interactions between the bound carotenoid pigments and their protein environment in the barb rami and barbules. This paper presents the first evidence of metabolically-derived methoxy-carotenoids in birds. 相似文献
956.
Sircar M Bradfield PF Aurrand-Lions M Fish RJ Alcaide P Yang L Newton G Lamont D Sehrawat S Mayadas T Liang TW Parkos CA Imhof BA Luscinskas FW 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(9):5879-5887
Endothelial cell junctional adhesion molecule (JAM)-C has been proposed to regulate neutrophil migration. In the current study, we used function-blocking mAbs against human JAM-C to determine its role in human leukocyte adhesion and transendothelial cell migration under flow conditions. JAM-C surface expression in HUVEC was uniformly low, and treatment with inflammatory cytokines TNF-alpha, IL-1beta, or LPS did not increase its surface expression as assessed by FACS analysis. By immunofluorescence microscopy, JAM-C staining showed sparse localization to cell-cell junctions on resting or cytokine-activated HUVEC. Surprisingly, staining of detergent-permeabilized HUVEC revealed a large intracellular pool of JAM-C that showed little colocalization with von Willebrand factor. Adhesion studies in an in vitro flow model showed that functional blocking JAM-C mAb alone had no inhibitory effect on polymorphonuclear leukocyte (PMN) adhesion or transmigration, whereas mAb to ICAM-1 significantly reduced transmigration. Interestingly, JAM-C-blocking mAbs synergized with a combination of PECAM-1, ICAM-1, and CD99-blocking mAbs to inhibit PMN transmigration. Overexpression of JAM-C by infection with a lentivirus JAM-C GFP fusion protein did not increase adhesion or extent of transmigration of PMN or evoke a role for JAM-C in transendothelial migration. These data suggest that JAM-C has a minimal role, if any, in PMN transmigration in this model and that ICAM-1 is the preferred endothelial-expressed ligand for PMN beta(2) integrins during transendothelial migration. 相似文献
957.
Wang L Surendran S Michals-Matalon K Bhatia G Tanskley S Koch R Grady J Tyring SK Stevens RC Guttler F Matalon R 《Genetic testing》2007,11(2):174-178
Tetrahydrobiopterin (BH4) is a co-factor that enhances the activity of other enzymes, and this co-factor level is found to be affected in phenylketonuria (PKU), an amino acid metabolism disorder. The present study was aimed at understanding the effect of BH4 on mutations in the regulatory domain of phenylalanine hydroxylase (PAH). Among 14 patients, 5 patients were classical PKU, 3 were atypical PKU, and 6 were mild PKU. All of these patients had at least one mutation in the regulatory domain. Patients were given 10 mg/kg BH4, and the response of blood phenylalanine (Phe) levels was monitored following treatment. The level of blood Phe decreased after BH4 treatment in all of the patients. These studies suggest that mutations in the regulatory domain also responded to BH4 even if the patient had classical PKU. 相似文献
958.
Francis PJ George S Schultz DW Rosner B Hamon S Ott J Weleber RG Klein ML Seddon JM 《Human heredity》2007,63(3-4):212-218
BACKGROUND AND AIMS: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western World. It is now evident that both genetic and environmental factors contribute to disease susceptibility. We tested the hypotheses that (a) a common coding SNP in the LOC387715 gene is associated with advanced AMD (geographic atrophy or choroidal neovascularization), and (b) that modifiable environmental exposures alter AMD susceptibility associated with this SNP. METHODS: A case-control association analysis was performed on participants (530 advanced AMD cases and 280 controls) ascertained as part of the multi-center Age-Related Eye Disease Study. AMD status was determined by the reading center from fundus photographs using the AREDS AMD grading categorization. Environmental risk factor exposure data was collected from participants whose DNA was also genotyped for the LOC387715 gene SNP rs10490924. Multivariate logistic regression analyses were performed. RESULTS AND CONCLUSIONS: The number of risk alleles at the LOC387715 SNP was associated with advanced AMD, with odds ratios (OR) = 3.0 (95% confidence interval (CI) 2.1-4.3) for the GT heterozygous genotype and OR = 12.1 (5.6-26.5) for the homozygous TT risk genotype, after controlling for demographic and behavioral risk factors. The LOC387715 SNP was associated with both forms of advanced AMD. Current cigarette smoking and body mass index were independently related to AMD, controlling for genotype. However, there was no statistical interaction between LOC387715 genotype and smoking with regard to advanced AMD development. 相似文献
959.
SER virus is a type 5 parainfluenza virus that does not exhibit syncytium formation, in contrast to most other paramyxoviruses. This property has been attributed, at least in part, to the presence of an extension of the cytoplasmic tail (CT) of the SER F protein, as truncations or mutations of this region resulted in enhanced fusion. In this study we used repeated passage to select for mutant SER viruses, which were found to be fusogenic. The mutant viruses replicated at levels comparable to or higher than the wild-type SER virus and caused plaque formation, in contrast to the wild-type virus which does not form plaques. The mutants differed strikingly in their plaque sizes. The F genes of mutant viruses were cloned and sequenced and shared some mutations, including a proline-to-leucine change at position 22 and an isoleucine-to-leucine substitution at position 191; other changes that were specific to each mutant were also found. The HN proteins of mutant viruses also showed mutations spanning the length of the protein whereas the M protein showed a consistent mutation, threonine to isoleucine, at position 129. The structure of the F protein was used to identify residues involved in the mutant phenotypes in terms of their location and proximity to heptad repeat domains. 相似文献
960.