全文获取类型
收费全文 | 2328篇 |
免费 | 226篇 |
国内免费 | 110篇 |
出版年
2024年 | 8篇 |
2023年 | 43篇 |
2022年 | 46篇 |
2021年 | 70篇 |
2020年 | 116篇 |
2019年 | 144篇 |
2018年 | 126篇 |
2017年 | 106篇 |
2016年 | 99篇 |
2015年 | 78篇 |
2014年 | 147篇 |
2013年 | 246篇 |
2012年 | 104篇 |
2011年 | 125篇 |
2010年 | 105篇 |
2009年 | 133篇 |
2008年 | 161篇 |
2007年 | 124篇 |
2006年 | 124篇 |
2005年 | 110篇 |
2004年 | 81篇 |
2003年 | 47篇 |
2002年 | 72篇 |
2001年 | 38篇 |
2000年 | 17篇 |
1999年 | 17篇 |
1998年 | 23篇 |
1997年 | 23篇 |
1996年 | 11篇 |
1995年 | 12篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 9篇 |
1991年 | 11篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1984年 | 9篇 |
1983年 | 4篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 5篇 |
1977年 | 2篇 |
1976年 | 4篇 |
1973年 | 2篇 |
1950年 | 1篇 |
排序方式: 共有2664条查询结果,搜索用时 15 毫秒
1.
In this work, incorporation of plasmid DNA, pre-complexed with PEI, into polyelectrolyte multilayers has been studied to further develop platforms for local gene delivery. Polyplex embedding in synthetic and naturally degradable architectures was efficient for transfection of human hepato-cellular carcinoma cells. 相似文献
2.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):837-839
Abstract Some diacid biodegradable synthesis of aziduthymidine (AZT) were synthesized and applied to production of about 60 different derivatives. 相似文献
3.
《Molecular cell》2021,81(20):4271-4286.e4
- Download : Download high-res image (250KB)
- Download : Download full-size image
4.
Mahsa Zahiri Maryam Babaei Khalil Abnous Seyed Mohammad Taghdisi Mohammad Ramezani Mona Alibolandi 《Journal of cellular physiology》2020,235(2):1036-1050
In this study, the chemical features of dendritic mesoporous silica nanoparticles (DMSNs) provided the opportunity to design a nanostructure with the capability to intelligently transport the payload to the tumor cells. In this regard, doxorubicin (DOX)-encapsulated DMSNs was electrostatically surface-coated with polycarboxylic acid dextran (PCAD) to provide biocompatible dextran-capped DMSNs (PCAD-DMSN@DOX) with controlled pH-dependent drug release. Moreover, a RNA aptamer against a cancer stem cell (CSC) marker, CD133 was covalently attached to the carboxyl groups of DEX to produce a CD133-PCAD-DMSN@DOX. Then, the fabricated nanosystem was utilized to efficiently deliver DOX to CD133+ colorectal cancer cells (HT29). The in vitro evaluation in terms of cellular uptake and cytotoxicity demonstrated that the CD133-PCAD-DMSN@DOX specifically targets HT29 as a CD133 overexpressed cancer cells confirmed by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The potentially promising intelligent-targeted platform suggests that targeted dextran-capped DMSNs may find impressive application in cancer therapy. 相似文献
5.
Reactive oxygen species (ROS) are involved in the pathophysiology of fulminant hepatic failure. Therefore, we developed polyethylene glycol-conjugated bovine serum albumin with multiple reduced thiols (PEG-BSA-SH) for the treatment of fulminant hepatic failure. As a long-circulating ROS scavenger, PEG-BSA-SH effectively scavenged highly reactive oxygen species and hydrogen peroxide in buffer solution. PEG-BSA-SH showed a long circulation time in the plasma after intravenous injection into mice. Fulminant hepatic failure was induced by intraperitoneal injection of lipopolysaccharide and d-galactosamine (LPS/d-GalN) into mice. The LPS/d-GalN-induced elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was significantly inhibited by a bolus intravenous injection of PEG-BSA-SH. Furthermore, the changes in hepatic lipid peroxide and hepatic blood flow were effectively suppressed by PEG-BSA-SH. In contrast, l-cysteine, glutathione, and dithiothreitol, three traditional reduced thiols, had no statistically significant effects on the serum levels of ALT or AST. These findings indicate that PEG-BSA-SH is a promising ROS scavenger and useful in the treatment of fulminant hepatic failure. 相似文献
6.
Joshua Seaberg Nicholas Flynn Amanda Cai Joshua D. Ramsey 《Biotechnology and bioengineering》2020,117(8):2504-2515
Therapeutic proteins are utilized in a variety of clinical applications, but side effects and rapid in vivo clearance still present hurdles. An approach that addresses both drawbacks is protein encapsulation within in a polymeric nanoparticle, which is effective but introduces the additional challenge of destabilizing the nanoparticle shell in clinically relevant locations. This study examined the effects of crosslinking self-assembled poly(l -lysine)-grafted-poly(ethylene glycol) nanoparticles with redox-responsive 3,3′-dithiobis(sulfosuccinimidyl propionate) (DTSSP) to achieve nanoparticle destabilization in a reductive environment. The polymer-protein nanoparticles (DTSSP NPs) were formed through electrostatic self-assembly and crosslinked with DTSSP, which contains a glutathione-reducible disulfide. As glutathione is upregulated in various cancers, DTSSP NPs could display destabilization within cancer cells. A library of DTSSP NPs was formed with varying copolymer to protein (C:P) and crosslinker to protein (X:P) mass ratios and characterized by size and encapsulation efficiency. DTSSP NPs with a 7:1 C:P ratio and 2:1 X:P ratio were further characterized by stability in the presence proteases and reducing agents. DTSSP NPs fully encapsulated the model protein and displayed 81% protein release when incubated with 5 mM dithiothreitol for 12 hr. This study contributes to understanding stimulus-responsive crosslinking of polymeric nanoparticles and could be foundational to clinical administration of therapeutic proteins. 相似文献
7.
The particle size characteristics of suspended sediment are of fundamental importance in understanding its role in a variety of environmental processes. Existing knowledge concerning the spatial and temporal variability of the grain size composition of suspended sediment is, however, relatively limited. At the global scale, major contrasts may exist between individual rivers in the calibre of their suspended load and this may be related to a number of controls including climate, catchment geology and basin scale. Any attempt to understand the precise relationship between the grain size characteristics of suspended sediment and those of its source material must also take account of the selectivity of erosion and delivery processes. A local case study undertaken by the authors in the 1500 km2 basin of the River Exe in Devon, UK is used to illustrate the considerable spatial variability that may occur within a relatively small area and the complexity of the associated controls.Available evidence concerning the temporal variability of the grain size characteristics of suspended sediment emphasises the diverse patterns of behaviour that may exist and the complexity of the controls involved. In some rivers the sediment may become coarser as flow increases, in others it may become finer, whilst in others it may exhibit a relatively constant grain size composition. Data from the local case study in the Exe basin are again used to highlight the considerable diversity in response to changing discharge that may occur within a relatively small area.Any attempt to understand the dynamics of sediment movement through a river system must also take account of the potential contrast between the ultimate and effective particle size distribution of suspended sediment in response to aggregation. Results from the Exe basin study indicate that even in rivers with relatively low solute concentrations, almost an order of magnitude difference may exist between the median particle size associated with the ultimate and effective grain size distributions. 相似文献
8.
Bruce Vondracek Wayne A. Wurtsbaugh Joseph J. Cech 《Environmental Biology of Fishes》1988,21(1):45-57
The allocation of energy to growth and reproduction, in relation to temperature and food availability, was investigated in
laboratory experiments with the mosquitofish,Gambusia affinis. At constant temperature of 20, 25 and 30°C and ad libitum feeding, specific growth rates increased with increasing temperature
at 1.7, 3.1 and 3.4% dry mass day−1, respectively. Growth rates in a cycling temperature regime (20–30°C,
) were faster than in a 25°C constant temperature. As temperature increased from 20 to 30°C, mean age at first reproduction
decreased from 191 to 56 days and brood size and mass of offspring increased significantly. Interbrood interval was also temperature
dependent; estimates at 25 and 30°C for females >1000 mg were 22.6 and 18.6 days, respectively. Interbrood interval could
not be calculated at 20°C. Although fitness was highest at 30°C, females at 25°C invested a greater proportion of surplus
energy (growth and reproduction) to reproduction (38%) than at 20 (17%) or 30°C (36%) during the 32-week study. Fish at cooler
temperatures began reproduction at a smaller size.
Where rations were controlled at low, medium, and ad libitum levels, somatic and gonadal growth increased with increasing
temperatures and food availability. The proportion of energy invested in reproduction was highest at 25°C for each comparable
ration level. Calculated energy budgets indicated that over the 10-week study, 17–22% of the food energy was invested in growth,
0–7% in reproduction, and 75–83% in respiration and excretory losses, depending on feeding and temperature conditions. 相似文献
9.
The construction and use of two novel transposon(Tn)-delivery vectors is described. These vectors carry Inc.W or Inc.N broad-host-range transfer functions cloned next to the narrow-host-range replicon of pBR329. The host specificities of pSLX10 and pSLX23 both complement and extend the host specificities of existing Tn delivery vectors. Plasmids pSLX10 and pSLX23 were shown to transfer at high frequency in intergeneric matings. The lux genes which are present on each vector permit the visual monitoring of transconjugants which have retained a Tn element, but are devoid of plasmid molecules. pSLX10 and pLSX23 were efficiently used to generate a range of auxotrophic mutants in various strains of Pseudomonas as well as to clone genes from Serratia liquefaciens. These vectors may have general applicability to identify and clone genes in a wide range of Gram-negative bacteria. 相似文献
10.
Summary A new culture method was used to study increases in wet and dry weight and soluble protein during normal development of the
transparent lens. Seven different media with more than ten different additives were tested for their effects on cultured lens
transparency.In vivo, rat lenses increased 53% in soluble protein content between 3 and 5.5 days of age. Only HL-1 serum-free medium containing
15 μg/ml insulin plus 1–2 ng/ml BB platelet-derived growth factor (PDGF), or 5–7 ng/ml epidermal growth factor (EGF) allowed
similar growthin vitro, during the same time period. Normal lens grwoth occurred in culture when fresh medium was delivered to lenses as a pulse
every 4–6 hours. Lenses decreased in dry weight and soluble protein content, and became opaque when the same medium was delivered
continuously. Lenses increased only 26% and 32% in soluble protein content when delivered pulses of HL-1 medium containing
BB PDGF or EGF in the absence of insulin. We suggest that pulsatile delivery of medium containing insulin and PDGF or EGF
stimulates lens growth during developmentin vitro. This pulsatile organ culture system is presented as a new approach for studying the effects of growth factors on cell proliferation,
differentiation, and receptor regulation in a developing tissue.
This work was supported by grants from EY-07031 and EY-04542 from the National Eye Institute and a grant from the Oculon Corporation.
Editor's statement This report documents an in vitro system that may mimic lens development and response to growth regulators
and hormones. The system may be useful for application to other organs and provide a foundation for cell and molecular level
analysis. 相似文献