全文获取类型
收费全文 | 538篇 |
免费 | 30篇 |
出版年
2024年 | 2篇 |
2022年 | 5篇 |
2021年 | 9篇 |
2020年 | 5篇 |
2019年 | 9篇 |
2018年 | 20篇 |
2017年 | 21篇 |
2016年 | 18篇 |
2015年 | 32篇 |
2014年 | 39篇 |
2013年 | 41篇 |
2012年 | 53篇 |
2011年 | 39篇 |
2010年 | 21篇 |
2009年 | 19篇 |
2008年 | 32篇 |
2007年 | 24篇 |
2006年 | 23篇 |
2005年 | 23篇 |
2004年 | 16篇 |
2003年 | 15篇 |
2002年 | 10篇 |
2001年 | 3篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 6篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1975年 | 7篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1972年 | 2篇 |
排序方式: 共有568条查询结果,搜索用时 15 毫秒
71.
Samuel Jalali Gurukumar K. Ramanathan Prasanna Tamarapu Parthasarathy Salman Aljubran Lakshmi Galam Asfiya Yunus Sara Garcia Ruan R. Cox Jr. Richard F. Lockey Narasaiah Kolliputi 《PloS one》2012,7(10)
Pulmonary Arterial Hypertension (PAH) is a progressive devastating disease characterized by excessive proliferation of the Pulmonary Arterial Smooth Muscle Cells (PASMCs). Studies suggest that PAH and cancers share an apoptosis-resistant state featuring excessive cell proliferation. MicroRNA-206 (miR-206) is known to regulate proliferation and is implicated in various types of cancers. However, the role of miR-206 in PAH has not been studied. In this study, it is hypothesized that miR-206 could play a role in the proliferation of PASMCs. In the present study, the expression patterns of miR-206 were investigated in normal and hypertensive mouse PASMCs. The effects of miR-206 in modulating cell proliferation, apoptosis and smooth muscle cell markers in human pulmonary artery smooth muscle cells (hPASMCs) were investigated in vitro. miR-206 expression in mouse PASMCs was correlated with an increase in right ventricular systolic pressure. Reduction of miR-206 levels in hPASMCs causes increased proliferation and reduced apoptosis and these effects were reversed by the overexpression of miR-206. miR-206 over expression also increased the levels of smooth muscle cell differentiation markers α-smooth muscle actin and calponin implicating its importance in the differentiation of SMCs. miR-206 overexpression down regulated Notch-3 expression, which is key a factor in PAH development. These results suggest that miR-206 is a potential regulator of proliferation, apoptosis and differentiation of PASMCs, and that it could be used as a novel treatment strategy in PAH. 相似文献
72.
Nadine?AME?van der BeekEmail author Juna?M?de Vries Marloes?LC?Hagemans Wim?CJ?Hop Marian?A?Kroos John?HJ?Wokke Marianne?de Visser Baziel?GM?van Engelen Jan?BM?Kuks Anneke?J?van der Kooi Nicolette?C?Notermans Karin?G?Faber Jan?JGM?Verschuuren Arnold?JJ?Reuser Ans?T?van der Ploeg Pieter?A?van Doorn 《Orphanet journal of rare diseases》2012,7(1):88
Background
Due partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression.Methods
We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3–6 months and analyzed using repeated-measures ANOVA.Results
Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2 years), skeletal muscle strength deteriorated significantly (mean declines of ?1.3% point/year for manual muscle testing and of ?2.6% points/year for hand-held dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary involvement (forced vital capacity in sitting position <80%) at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast.Conclusions
Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when.73.
74.
The rates of degradation of total soluble proteins in the free-living nematode, , have been estimated by following the loss of acid-insoluble insoluble radioactivity from protein during a nonradioactive chase period after initial labeling with [35S]methionine. These proteins appear to lose label kinetically as a homogeneous class in age-synchronized nematode populations. However, proteins are degraded more slowly in senescent cultures than in young cultures. Protein degradation rates decline progressively during nematode aging. These findings suggest that the protein degradative system in T. aceti may become partially defective with advancing age which may result in the accumulation of aberrant protein molecules in senescent organisms. 相似文献
75.
Valerio Chiroli Minerva R. Batugo Stefano Biondi Annalisa Bonfanti Stefania Brambilla David C. Gale Lin Li Daniela Miglietta Fabio Nicoli Ganesh A. Prasanna Daniela Ronchetti William F. Vernier Wesley K.M. Chong 《Bioorganic & medicinal chemistry letters》2009,19(10):2785-2788
A novel class of timolol derivatives with nitric oxide (NO)-donating moieties achieved chemical stability yet under physiologically relevant conditions released timolol and NO. Hindered esters A were designed and synthesized, whose ‘triggered’ release relied on enzymatic hydrolysis of the nitrate ester in A to B, that in turn cyclized to liberate timolol. 相似文献
76.
Rhitu Rai Prasanta K. Dash B. M. Prasanna Aqbal Singh 《World journal of microbiology & biotechnology》2007,23(6):853-858
The genotypic diversity of indigenous bacterial endophytes within stem of tropical maize (Zea mays L.) was determined in field and greenhouse experiments. Strains were isolated from stem tissues of a tropical maize cultivar
(PEHM-1) by trituration and surface disinfestation and their population dynamics was determined. Endophytes were found in
most of the growing season at populations ranging from 1.36–6.12 × 105 colony-forming units per gram fresh weight (c.f.u./gm fw) of stem. Analysis of these bacterial endophytes using Gas Chromatography—Fatty
Acid Methyl Ester (GC-FAME) led to the identification of Bacillus pumilus, B. subtilis, Pseudomonas aeruginosa and P. fluorescens as the relatively more predominant group of bacterial species residing in maize stem. When the maize seedlings grown in a
greenhouse were inoculated with these four isolates individually, their population densities decreased (1.6–3.1 × 105 c.f.u./gm fw of stem) as compared to the field-grown maize (1.8–3.8 × 105 c.f.u./gm fw of stem). The highest persistence, however, was recovered in the case of B. subtilis with a population density of 3.1 × 105 c.f.u./gm fw of stem tissue on 28 days after emergence (DAE). This is the first report on population dynamics of bacterial
endophytes from tropical maize and the results establish that symptomless populations of bacteria exist in the maize stem. 相似文献
77.
Interfacial Effects of Tin Oxide Atomic Layer Deposition in Metal Halide Perovskite Photovoltaics 下载免费PDF全文
Axel F. Palmstrom James A. Raiford Rohit Prasanna Kevin A. Bush Melany Sponseller Rongrong Cheacharoen Maxmillian C. Minichetti David S. Bergsman Tomas Leijtens Hsin‐Ping Wang Vladimir Bulović Michael D. McGehee Stacey F. Bent 《Liver Transplantation》2018,8(23)
Metal halide perovskites offer a wide and tunable bandgap, making them promising candidates for top‐cell absorbers in tandem photovoltaics. In this work, the authors aim to understand the atomic layer deposition (ALD) precursor–perovskite interactions of the tin oxide ALD system and the role of organic fullerenes at the perovskite–tin oxide interface while establishing a framework for developing alternative perovskite‐compatible ALD processes in the future. It is shown, in the case of tin oxide ALD growth with tetrakis(dimethylamino)tin(IV) and water on FA0.83Cs0.17Pb(I0.83Br0.17)3 perovskite, that perovskite stability is most sensitive to metal–organic exposure at elevated temperatures with an onset near 110 °C, resulting in removal of the formamidinium cation. Transitioning from ALD to pulsed‐chemical vapor deposition tin oxide growth can minimize the degradation effects. Investigation of fullerenes at the perovskite interface shows that thin fullerene layers offer minor improvements to perovskite stability under ALD conditions, but significant enhancement in carrier extraction. Fullerene materials are undesirable due to fabrication cost and poor mechanical stability. Compositional tuning of the perovskite material can improve the fullerene‐free device performance. This method is demonstrated with a bromine‐rich perovskite phase to enable an 8.2% efficient perovskite device with all‐inorganic extraction layers. 相似文献
78.
Structural analysis of protein tyrosine phosphatase 1B reveals potentially druggable allosteric binding sites 下载免费PDF全文
Catalytic proteins such as human protein tyrosine phosphatase 1B (PTP1B), with conserved and highly polar active sites, warrant the discovery of druggable nonactive sites, such as allosteric sites, and potentially, therapeutic small molecules that can bind to these sites. Catalyzing the dephosphorylation of numerous substrates, PTP1B is physiologically important in intracellular signal transduction pathways in diverse cell types and tissues. Aberrant PTP1B is associated with obesity, diabetes, cancers, and neurodegenerative disorders. Utilizing clustering methods (based on root mean square deviation, principal component analysis, nonnegative matrix factorization, and independent component analysis), we have examined multiple PTP1B structures. Using the resulting representative structures in different conformational states, we determined consensus clustroids and used them to identify both known and novel binding sites, some of which are potentially allosteric. We report several lead compounds that could potentially bind to the novel PTP1B binding sites and can be further optimized. Considering the possibility for drug repurposing, we discovered homologous binding sites in other proteins, with ligands that could potentially bind to the novel PTP1B binding sites. 相似文献
79.
Prasanna L. Chintapalli J. P. Moss Kiran K. Sharma J. K. Bhalla 《In vitro cellular & developmental biology. Plant》1997,33(1):30-37
Summary The present study is an attempt to exploit somaclonal variation for the varietal improvement of pigeonpea [Cajanus cajan (L) Millsp.]. The pigeonpea plants were regenerated from cotyledon explants, and their progeny was screened for variability.
The regenerated R1 plants exhibited a spectrum of alterations in floral morphology and architecture that were absent in the
control population. The field-sown R2 plants segregated for traits such as flower color, leaf shape, seed size, color and
strophiolation, flowering habit, and fertility. Tissue culture produced different mutational events resulting in both dominant
and recessive alleles. Significant variation was observed for plant height, seed mass, and damage due to the insect pest Helicoverpa armigera. The R3 plants, obtained from seed of R2 generation selected for traits such as white seed coat, strophiolation, reduced
plant height, seed mass and low damage due to Helicoverpa, maintained the traits when compared with the seed-derived control populations. The results indicate a definite gene for
white seed coat and the possibility of additional genes for pest tolerance and high seed mass in an adapted background.
Submitted as Journal Article No. 1906 by International Crops Research Institute for the Semi-Arid Tropics (ICRISAT). 相似文献
80.
Aparna Sharma Anu Mary Varghese Kalyan Vijaylakshmi Rajendrarao Sumitha V. K. Prasanna S. Shruthi B. K. Chandrasekhar Sagar Keshava K. Datta Harsha Gowda Atchayaram Nalini Phalguni Anand Alladi Rita Christopher Talakad N. Sathyaprabha Trichur R. Raju M. M. Srinivas Bharath 《Neurochemical research》2016,41(5):965-984
In our laboratory, we have developed (1) an in vitro model of sporadic Amyotrophic Lateral Sclerosis (sALS) involving exposure of motor neurons to cerebrospinal fluid (CSF) from sALS patients and (2) an in vivo model involving intrathecal injection of sALS-CSF into rat pups. In the current study, we observed that spinal cord extract from the in vivo sALS model displayed elevated reactive oxygen species (ROS) and mitochondrial dysfunction. Quantitative proteomic analysis of sub-cellular fractions from spinal cord of the in vivo sALS model revealed down-regulation of 35 mitochondrial proteins and 4 lysosomal proteins. Many of the down-regulated mitochondrial proteins contribute to alterations in respiratory chain complexes and organellar morphology. Down-regulated lysosomal proteins Hexosaminidase, Sialidase and Aryl sulfatase also displayed lowered enzyme activity, thus validating the mass spectrometry data. Proteomic analysis and validation by western blot indicated that sALS-CSF induced the over-expression of the pro-apoptotic mitochondrial protein BNIP3L. In the in vitro model, sALS-CSF induced neurotoxicity and elevated ROS, while it lowered the mitochondrial membrane potential in rat spinal cord mitochondria in the in vivo model. Ultra structural alterations were evident in mitochondria of cultured motor neurons exposed to ALS-CSF. These observations indicate the first line evidence that sALS-CSF mediated mitochondrial and lysosomal defects collectively contribute to the pathogenesis underlying sALS. 相似文献