全文获取类型
收费全文 | 947篇 |
免费 | 44篇 |
出版年
2023年 | 10篇 |
2022年 | 27篇 |
2021年 | 29篇 |
2020年 | 12篇 |
2019年 | 24篇 |
2018年 | 29篇 |
2017年 | 20篇 |
2016年 | 30篇 |
2015年 | 38篇 |
2014年 | 51篇 |
2013年 | 69篇 |
2012年 | 87篇 |
2011年 | 81篇 |
2010年 | 34篇 |
2009年 | 30篇 |
2008年 | 42篇 |
2007年 | 44篇 |
2006年 | 38篇 |
2005年 | 22篇 |
2004年 | 21篇 |
2003年 | 25篇 |
2002年 | 16篇 |
2001年 | 19篇 |
2000年 | 17篇 |
1999年 | 13篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1993年 | 4篇 |
1992年 | 11篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 12篇 |
1984年 | 8篇 |
1983年 | 3篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1973年 | 6篇 |
1971年 | 4篇 |
排序方式: 共有991条查询结果,搜索用时 15 毫秒
81.
The design, synthesis, and application of novel biodegradable and biocompatible pentablock (PB) copolymers, i.e., polyglycolic acid-polycaprolactone-polyethylene glycol-polycaprolactone-polyglycolic acid (PGA-PCL-PEG-PCL-PGA) and polylactic acid-polycaprolactone-polyethylene glycol-polycaprolactone-polylactic acid (PLA-PCL-PEG-PCL-PLA) for sustained protein delivery, are reported. The PB copolymers can be engineered to generate sustained delivery of protein therapeutics to the posterior segment of the eye. PB copolymers with different block arrangements and molecular weights were synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance (1H-NMR), gel permeation chromatography (GPC), and X-ray diffraction (XRD) spectroscopy. Immunoglobulin G (IgG) was selected as a model protein due to its structural similarity to bevacizumab. The influence of polymer molecular weight, composition, and isomerism on formulation parameters such as entrapment efficiency, drug loading, and in vitro release profile was delineated. Crystallinity and molecular weight of copolymers exhibited a substantial effect on formulation parameters. A secondary structure of released IgG was confirmed by circular dichroism (CD) spectroscopy. In vitro cytotoxicity, cell viability, and biocompatibility studies performed on human retinal pigment epithelial cells (ARPE-19) and/or macrophage cell line (RAW 264.7) demonstrated PB copolymers to be excellent biomaterials. Novel PB polymers may be the answer to the unmet need of a sustained release protein formulation.KEY WORDS: block copolymers, controlled drug delivery, IgG, intravitreal, nanoparticles, ocular delivery, pentablock copolymers, posterior segment, protein therapeutics, sustained drug delivery 相似文献
82.
A noteworthy metabolic signature accompanying oil body (OB) biogenesis during oilseed development is associated with the modulation of the oil body membranes proteins. Present work focuses on 2-dimensional polyacrylamide gel electrophoresis (2-D PAGE)-based analysis of the temporal changes in the OB membrane proteins analyzed by LC-MS/MS accompanying the onset of desiccation (20–30 d after anthesis; DAA) in the developing seeds of sunflower (Helianthus annuus L.). Protein spots unique to 20–30 DAA stages were picked up from 2-D gels for identification and the identified proteins were categorized into 7 functional classes. These include proteins involved in energy metabolism, reactive oxygen scavenging, proteolysis and protein turnover, signaling, oleosin and oil body biogenesis-associated proteins, desiccation and cytoskeleton. At 30 DAA stage, exclusive expressions of enzymes belonging to energy metabolism, desiccation and cytoskeleton were evident which indicated an increase in the metabolic and enzymatic activity in the cells at this stage of seed development (seed filling). Increased expression of cruciferina-like protein and dehydrin at 30 DAA stage marks the onset of desiccation. The data has been analyzed and discussed to highlight desiccation stage-associated metabolic events during oilseed development. 相似文献
83.
84.
Yolanda Stypula-Cyrus Nikhil N. Mutyal Mart Dela Cruz Dhananjay P. Kunte Andrew J. Radosevich Ramesh Wali Hemant K. Roy Vadim Backman 《FEBS letters》2014
End-binding protein (EB1) is a microtubule protein that binds to the tumor suppressor adenomatous polyposis coli (APC). While EB1 is implicated as a potential oncogene, its role in cancer progression is unknown. Therefore, we analyzed EB1/APC expression at the earliest stages of colorectal carcinogenesis and in the uninvolved mucosa (“field effect”) of human and animal tissue. We also performed siRNA-knockdown in colon cancer cell lines. EB1 is up-regulated in early and field carcinogenesis in the colon, and the cellular/nano-architectural effect of EB1 knockdown depended on the genetic context. Thus, dysregulation of EB1 is an important early event in colon carcinogenesis. 相似文献
85.
Prabodh K. Bajpai Ashish R. Warghat Ram Kumar Sharma Ashish Yadav Anil K. Thakur Ravi B. Srivastava Tsering Stobdan 《Biochemical genetics》2014,52(3-4):137-152
Sequence-related amplified polymorphism markers were used to assess the genetic structure in three natural populations of Morus alba from trans-Himalaya. Multilocation sampling was conducted across 14 collection sites. The overall genetic diversity estimates were high: percentage polymorphic loci 89.66%, Nei’s gene diversity 0.2286, and Shannon’s information index 0.2175. At a regional level, partitioning of variability assessed using analysis of molecular variance (AMOVA), revealed 80% variation within and 20% among collection sites. Pattern appeared in STRUCTURE, BARRIER, and AMOVA, clearly demonstrating gene flow between the Indus and Suru populations and a geographic barrier between the Indus-Suru and Nubra populations, which effectively hinders gene flow. The results showed significant genetic differentiation, population structure, high to restricted gene flow, and high genetic diversity. The assumption that samples collected from the three valleys represent three different populations does not hold true. The fragmentation present in trans-Himalaya was more natural and less anthropogenic. 相似文献
86.
In India, about 0.86 million people is engaged in pulling cycle rickshaws as occupation. There is no anthropometric data of cycle rickshaw pullers although data is available for Indian population. The objective of the study was to collect anthropometric data of the cycle rickshaw pullers so that these could be utilized for redesigning a cycle rickshaw. Anthropometric data for 34 body measurements were recorded from 880 rickshaw pullers (age 18 to 66 years) of four different places in India. The mean values of different standing heights, different lengths and breadths of cycle rickshaw pullers were significantly lower compared with Indian population. However, there was no significant difference in erect sitting height. The outcome of the research project is beneficial for the manufacturers of cycle rickshaws and similar products well as users of such products, including rickshaw pullers. The manufacturers would be able to use the data for fabricating newer models of cycle rickshaws which would be more compatible for rickshaw pullers as well as passengers. 相似文献
87.
Four different bacterial strains were isolated from pulp and paper mill sludge in which one alkalotolerant isolate (LP1) having
higher capability to remove color and lignin, was identified as Bacillus sp. by 16S RNA sequencing. Optimization of process parameters for decolorization was initially performed to select growth
factors which were further substantiated by Taguchi approach in which seven factors, % carbon, % black liquor, duration, pH,
temperature, stirring and inoculum size, at two levels, applying L-8 orthogonal array were taken. Maximum color was removed
at pH 8, temperature 35°C, stirring 200 rpm, sucrose (2.5%), 48 h, 5% (w/v) inoculum size and 10% black liquor. After optimization
2-fold increase in color and lignin removal from 25–69% and 28–53%, respectively, indicated significance of Taguchi approach
in decolorization and delignification of lignin in pulp and paper mill effluent. Enzymes involved in the process of decolorization
of effluent were found to be xylanase (54 U/ml) and manganese peroxidase (28 U/ml). Treated effluent was also evaluated for
toxicity by Comet assay using Saccharomyces cerevisiae MTCC 36 as model organism, which indicated 58% reduction after treatment by bacterium. 相似文献
88.
Alexander Weng Kristina Jenett-Siems Peter Schmieder Diana Bachran Christopher Bachran Cornelia Görick Mayank Thakur Hendrik Fuchs Matthias F. Melzig 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(7-8):713-718
Saponinum album (Merck), which is a crude mixture of saponins from Gypsophila paniculata L., was shown to improve the anti cancer therapy when used in vivo in combination with saporin-based targeted toxins. Unfortunately saponinum album cannot be used for further development since Merck has ceased its production in the 1990s. As pure saponins are mandatory for use in medical purposes we developed a convenient method for saponin isolation directly from the roots of Gypsophila paniculata L. The developed method is rapid, cheap and scaling up is also possible. By combining dialysis and HPLC three saponins were isolated in a one-step procedure. Chemical structures of the purified saponins were characterized by extensive one and two-dimensional NMR-spectroscopy and by using ESI-TOF-MS. The biological activities of the purified saponins were also investigated. The method presented herein enabled a rapid and cheap isolation of saponins for tumour therapy. 相似文献
89.
We report here that, during periodical surveys of insects inhabiting diverse habitats for the collection of entomopathogenic
fungi; a large number of isolates were recovered belonging to seven species, from various regions of Madhya Pradesh and Chhattisgarh
forest areas and agricultural fields. The most common entomopathogenic fungi such as Beauveria bassiana, Nomuraea rileyi, Paecilomyces farinosus and Paecilomyces fumosoroseus were found to infect various insect hosts species naturally viz. Hyblaea puera, Eutectona machaeralis, Diachrysia orichalcea, Spodoptera litura, and few new insect hosts of these fungal pathogens among Indian insect population were collected for the first time from
Central India, such as beetles of Agrilus species, hairy caterpillars of Lymantria species. The isolation, identification, maintenance and pathogenicity assay of these isolates was performed prior to deposition
in culture collection center. 相似文献
90.
Zhang K Aruva MR Shanthly N Cardi CA Patel CA Rattan S Cesarone G Wickstrom E Thakur ML 《Regulatory peptides》2007,144(1-3):91-100
Vasoactive intestinal peptide and pituitary adenylate cyclase activating peptide have high affinity for VPAC1, VPAC2 and PAC1 receptors overexpressed on human cancer cells. Four potent analogues of these peptides, TP3939, TP3982, TP4200 and TP3805 were labeled with (64)Cu and evaluated ex vivo and in vivo to asses their biological activity and receptor specificity. The ultimate goal is to utilize (64)Cu analogues for positron emission tomography (PET) imaging of breast cancers in humans. Radiochemical purity of each analogue was >92%. The muscle relaxivity assay revealed IC(50) to be 5.3x10(-8) M, 4.4x10(-8) M, 8.1x10(-8) M, 8.1x10(-9) M and Kd values determined by receptor specific cell binding assays were 3.3 nM, 0.33 nM, 0.2 nM and 0.72 nM for TP3805, TP3939, TP3982, and TP4200 respectively. The receptor affinity, using human breast cancer tissues, was 10.93 times greater than normal breast tissues. RT-PCR confirmed increased VPAC1 receptor expression on human breast tumor cells over normal cells and corroborated with autoradiography data. The blood clearance was rapid and in vivo translocation of (64)Cu to plasma protein was <15%. Data demonstrate that these analogues are potent, have uncompromised biological activity and are worthy of further evaluation for accurate PET imaging of human breast cancers and in determining malignant and benign lesions. 相似文献