全文获取类型
收费全文 | 4098篇 |
免费 | 247篇 |
国内免费 | 486篇 |
出版年
2023年 | 74篇 |
2022年 | 76篇 |
2021年 | 102篇 |
2020年 | 132篇 |
2019年 | 166篇 |
2018年 | 140篇 |
2017年 | 151篇 |
2016年 | 120篇 |
2015年 | 119篇 |
2014年 | 195篇 |
2013年 | 302篇 |
2012年 | 135篇 |
2011年 | 244篇 |
2010年 | 152篇 |
2009年 | 276篇 |
2008年 | 244篇 |
2007年 | 255篇 |
2006年 | 218篇 |
2005年 | 170篇 |
2004年 | 181篇 |
2003年 | 121篇 |
2002年 | 101篇 |
2001年 | 72篇 |
2000年 | 86篇 |
1999年 | 82篇 |
1998年 | 76篇 |
1997年 | 75篇 |
1996年 | 66篇 |
1995年 | 73篇 |
1994年 | 41篇 |
1993年 | 51篇 |
1992年 | 60篇 |
1991年 | 39篇 |
1990年 | 29篇 |
1989年 | 31篇 |
1988年 | 25篇 |
1987年 | 30篇 |
1986年 | 29篇 |
1985年 | 43篇 |
1984年 | 34篇 |
1983年 | 21篇 |
1982年 | 34篇 |
1981年 | 36篇 |
1980年 | 28篇 |
1979年 | 30篇 |
1978年 | 20篇 |
1977年 | 17篇 |
1976年 | 5篇 |
1974年 | 7篇 |
1973年 | 4篇 |
排序方式: 共有4831条查询结果,搜索用时 46 毫秒
1.
《Bioorganic & medicinal chemistry letters》2014,24(7):1724-1729
A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus epidermidis (MRSE). 相似文献
2.
《Cryobiology》2018
The objective of this study was to evaluate the use of Afp1m as a cryopreservative agent for skin by examining the transplanted skin histological architecture and mechanical properties following subzero cryopreservation. Thirty four (34) rats with an average weight of 208 ± 31 g (mean ± SD), were used. Twenty four (n = 24) rats were equally divided into four groups: (i) immediate non-cryopreserved skin autografts (onto same site), (ii) immediate non-cryopreserved skin autografts (onto different sites), (iii) skin autografts cryopreserved with glycerol for 72 h and (iv) skin autografts cryopreserved with Afp1m for 72 h at −4 °C. Rounded shaped full-thickness 1.5–2.5 cm in diameter skin was excised from backs of rats for the autograft transplantation. Non-cryopreserved or cryopreserved auto skin graft were positioned onto the wound defects and stitched. Non-transplanted cryopreserved and non-cryopreserved skin strips from other ten rats (n = 10) were allowed for comparative biomechanical test. All skin grafts were subjected to histological and mechanical examinations at the end of day 21. Histological results revealed that tissue architecture especially the epidermal integrity and dermal-epidermal junction of the Afp1m cryopreserved skin grafts exhibited better histological appearance, good preservation of tissue architecture and structural integrity than glycerolized skin. However, there was no significant difference among these groups in other histological criteria. There were no significant differences among the 4 groups in skin graft mechanical properties namely maximum load. In conclusion, Afp1m were found to be able to preserve the microstructure as well as the viability and function of the skin destined for skin transplantation when was kept at −4 °C for 72 h. 相似文献
3.
Santosh R. D'Mello Fabio Aglieco Melanie R. Roberts Kristin Borodezt John W. Haycock 《Journal of neurochemistry》1998,70(5):1809-1818
Abstract: Cultured cerebellar granule neurons undergo apoptosis when switched from a medium containing depolarizing levels of K+ (25 mM KCI) to medium containing lower levels of K+ (5 mM KCI). We used this paradigm to investigate the role of caspases in the death process. Two broad-spectrum caspase inhibitors, tert-butoxycarbonyl-Asp·(O-methyl)·fluoromethyl ketone and benzyloxycarbonyl-Val-Ala-Asp·fluoromethyl ketone, significantly reduced cell death (90 and 60%, respectively) at relatively low concentrations (10–25 µM), suggesting that caspase activation is involved in the apoptotic process. DNA fragmentation, a hallmark of apoptosis, was also reduced by these caspase inhibitors, suggesting that caspase activation occurred upstream of DNA cleavage in the sequence of events leading to cell death. As a step toward identifying the caspase(s) involved, the effects of N-acetyl Tyr-Val-Ala-Asp·chloromethyl ketone (YVAD·cmk), an interleukin-1β converting enzyme-preferring inhibitor, and N-acetyl Asp-Glu-Val-Asp·fluoromethyl ketone (DEVD·fmk), a CPP32-preferring inhibitor, were also evaluated. YVAD·cmk provided only modest (<20%) protection and only at the highest concentration (100 µM) tested, suggesting that interleukin-1β converting enzyme and/or closely related caspases were not involved. In comparison, DEVD·fmk inhibited cell death by up to 50%. Western blot analyses, however, failed to detect an increase in processing/activation of CPP32 or in the proteolysis of a CPP32 substrate, poly(ADP-ribose) polymerase, during the induction of apoptosis in granule neurons. Similarly, the levels of Nedd2, a caspase that is highly expressed in the brain and that is partially inhibited by DEVD·fmk, also remained unaffected in apoptotic neurons undergoing apoptosis. These results suggest that a DEVD-sensitive caspase other than CPP32 or Nedd2 mediates the induction of apoptosis in K+-deprived granule neurons. 相似文献
4.
Tippawan Siritientong Walter Bonani Antonella Motta Claudio Migliaresi 《Bioscience, biotechnology, and biochemistry》2016,80(2):241-249
Sericin was extracted from three strains of Thai Bombyx mori silk cocoons (white shell Chul1/1, greenish shell Chul3/2, and yellow shell Chul4/2) by a high-pressure and high-temperature technique. The characteristics of sericin extracted from different fractions (15, 45, and 60 min extraction process) were compared. No differences in amino acid composition were observed among the three fractions. For all silk strains, sericin extracted from a 15-min process presented the highest molecular weight. The biological potential of the different sericin samples as a bioadditive for 3T3 fibroblast cells was assessed. When comparing sericin extracted from three silk strains, sericin fractions extracted from Chul4/2 improved cell proliferation, while sericin from Chul 1/1 activated Type I collagen production to the highest extent. This study allows the natural variability of sericin obtained from different sources and extraction conditions to be addressed and provides clues for the selection of sericin sources. 相似文献
5.
Maria Weinert Tharakeswari Selvakumar Travis S. Tierney Kambiz N. Alavian 《Journal of visualized experiments : JoVE》2015,(96)
Degeneration of mesencephalic dopaminergic (mesDA) neurons is the pathological hallmark of Parkinson’s diseae. Study of the biological processes involved in physiological functions and vulnerability and death of these neurons is imparative to understanding the underlying causes and unraveling the cure for this common neurodegenerative disorder. Primary cultures of mesDA neurons provide a tool for investigation of the molecular, biochemical and electrophysiological properties, in order to understand the development, long-term survival and degeneration of these neurons during the course of disease. Here we present a detailed method for the isolation, culturing and maintenance of midbrain dopaminergic neurons from E12.5 mouse (or E14.5 rat) embryos. Optimized cell culture conditions in this protocol result in presence of axonal and dendritic projections, synaptic connections and other neuronal morphological properties, which make the cultures suitable for study of the physiological, cell biological and molecular characteristics of this neuronal population. 相似文献
6.
The muscle collagen of marine prawn,Penaeus indicus, was isolated by limited pepsin digestion. Based on selective salt precipitation, amino acid composition and gel electrophoretic
pattern, the major collagen was found to be a homotrimer of á 1 chain, similar to type V collagen of vertebrates. Electron
microscopy of reconstituted fibrils, made for the first time from a crustacean species, revealed a characteristic 64 nm periodicity.
Biochemical studies indicate a less than normal amount of associated carbohydrates and an increased alanine content The major
collagen had a denatu ration temperature of 37°C with an intrinsic viscosity of 11.3 dl/g. Spectral characteristics of the
major collagen were studied. Results suggest the presence of genetically distinct collagen types and acid resistant cross
links in crustacean muscle. 相似文献
7.
《Bioorganic & medicinal chemistry》2016,24(21):5431-5439
Heat shock protein 90 (Hsp90) as a molecular target for oncology therapeutics has attracted much attention in the last decade. The Hsp90 multichaperone complex has important roles in the growth and/or survival of cancer cells. Cdc37, as a cochaperone, associates kinase clients to Hsp90 and promotes the development of malignant tumors. Disrupting the Hsp90–Cdc37 interaction provides an alternative strategy to inhibit the function of Hsp90 for cancer therapy. Celastrol, as a natural product, can disrupt the Hsp90–Cdc37 interaction and induce degradation of kinase clients. The study conducted here attempted to elucidate the structure–activity relationship of celastrol derivatives as Hsp90–Cdc37 disruptors and to improve the druglike properties. 23 celastrol derivatives were designed, synthesized, and the biological activities and physicochemical properties were determined. The derivative CEL20 showed improved Hsp90–Cdc37 disruption activity, anti-proliferative activities as well as druglike properties. Additionally, CEL20 induced clients degradation, cell cycle arrest and apoptosis in Panc-1 cells. This study can provide reference for the discovery of novel Hsp90–Cdc37 disruptors. 相似文献
8.
Tillage is known to potentially affect soil quality in various ways. In this study, a soil quality index (SQI) was developed by quantifying several soil attributes either sensitive or insensitive to physical disturbance, using factor analysis as a dimension reduction technique, in order to discriminate different tillage systems. Soil properties including physical (MWD), chemical (pH, organic C, total N, available P and POM contents) and microbial (MBC, MBN, PCM, PNM and three enzymes) parameters were measured to establish a minimum data set (MDS) for the assessment of overall SQI. The soil attributes were determined on samples (0–20 cm depth) collected under moldboard (MP) and disk (DP) plows as conventional tillage (CT), and rotary (RP) and chisel (CP) plows as reduced tillage (RT) systems with a similar plant C input rate and cover crop over a period of six years (2005–2011) in a semi-arid calcareous soil (Calcixerepts) from Central Iran. Results indicated a clear difference in soil quality among the tillage systems with a significant increase of SQI under RT over time, particularly under CP practices. Although RT improved most soil microbial attributes, not all attributes contributed to SQI because of their close interrelationship. The final SQI consisted only of geometric mean of microbial activity (GMA, the square root of the product of PCM and PNM) and geometric mean of enzyme activity (GME, the cube root of the product of enzyme activities). Soil GME and GMA were found to be as key indicators contributing 55% and 36% to SQI, respectively. Therefore, the GME and GMA were the most important indicators effectively discriminating tillage systems, and could be used to monitor the enhancement of soil quality under RT in this semiarid environment. The influence of tillage year on SQI was greater than that of tillage practices. In conclusion, RT systems were characterized by a higher value of SQI, suggesting a good recovery of soil capacity and functions after abandoning CT in the studied area. Smallholder farmers should therefore be aware of the potential for high soil quality in future as a result of continuing RT systems, especially with surface tillage using CP practices. 相似文献
9.
A series of Rh(III) mixed ligand polypyridine type complexes have been prepared. Complexes of the form [Rh(L)2(L′)]n+, where n=2/3, L=2,2′-bipyridine (bpy)/1,10-phenanthroline (phen) and L′=3-(pyridin-2-yl)-1,2,4-triazole (Hpytr), 1-methyl-3-(pyridin-2-yl)-1,2,4-triazole (1M3pytr), 4-methyl-3-(pyridin-2-yl)-1,2,4-triazole (4Mpytr), 3,5-bis(pyridin-2-yl)-1,2,4-triazole (Hbpt), 4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole (NH2bpt) and 3-(pyridin-2-yl)-5-phenyl-1,2,4-triazole (HPhpytr), have been prepared and their synthesis and characterisation are reported. Crystals of [Rh(bpy)2(Phpytr)](PF6)2 and [Rh(phen)2(NHbpt)](PF6)2 were obtained and their structures determined. Analysis of X-ray crystallographic data showed that coordination of the metal centre in [Rh(phen)2(NHbpt)](PF6)2 occurs via the amine moiety and a nitrogen of the pyridine ring. NMR studies illustrated that coordination to the NH2bpt ligand was also possible via a nitrogen of the triazole ring and the pyridine ring forming the complex [Rh(phen)2(NH2bpt)](PF6)3. The absorption and emission properties of the complexes studied were found to be π-π* in nature and preliminary evidence suggests that all complexes with the exception of [Rh(phen)2(NHbpt)](PF6)2 and [Rh(bpy)2(NHbpt)](PF6)2 are dual emitting at 77 K. 相似文献
10.
Bioturbation by benthic infauna has important implications for the fate of contaminants as well as for changes to the sediment
structure, chemistry and transport characteristics. There is an extensive literature dealing with the influence of sedimentary
variables on the structure and function of infaunal marine and estuarine organisms but less is known of the converse, the
influence of biota on sedimentary structure. Although some work has been carried out regarding spatial and temporal patterns
of bioturbation, little attention has been given to the effects of pollution. The paper gives a framework of animal sediment
relationships in an intertidal environment and discusses the general role of macrofauna in structuring and modifying sedimentary
features. A brief outline of the various techniques used for quantifying the degree of bioturbation is given and some of these
techniques have then been used to demonstrate the effect of a petrochemical discharge on the bioturbation potential of intertidal
communities in the Humber estuary, eastern England. These studies indicate an increase in bioturbation with increasing distance
from the source of pollution, not only because of differences in abundance, animal size and depth of activity but also because
of the difference in species composition between the communities. As a means of interpreting the responses, the species present
have been broadly classified in terms of their feeding strategy and sediment modification potential. The paper concludes by
discussing the potential impact, in terms of effect on sediment transport, of selectively removing the different guilds (by
pollution).
Received: 8 February 1999 / Received in revised form: 10 May 1999 / Accepted: 14 May 1999 相似文献