全文获取类型
收费全文 | 3984篇 |
免费 | 250篇 |
国内免费 | 3篇 |
专业分类
4237篇 |
出版年
2023年 | 21篇 |
2022年 | 53篇 |
2021年 | 94篇 |
2020年 | 64篇 |
2019年 | 73篇 |
2018年 | 122篇 |
2017年 | 91篇 |
2016年 | 166篇 |
2015年 | 216篇 |
2014年 | 214篇 |
2013年 | 320篇 |
2012年 | 343篇 |
2011年 | 325篇 |
2010年 | 219篇 |
2009年 | 144篇 |
2008年 | 241篇 |
2007年 | 233篇 |
2006年 | 219篇 |
2005年 | 196篇 |
2004年 | 169篇 |
2003年 | 152篇 |
2002年 | 151篇 |
2001年 | 31篇 |
2000年 | 17篇 |
1999年 | 30篇 |
1998年 | 34篇 |
1997年 | 28篇 |
1996年 | 24篇 |
1995年 | 24篇 |
1994年 | 19篇 |
1993年 | 19篇 |
1992年 | 28篇 |
1991年 | 17篇 |
1990年 | 11篇 |
1989年 | 12篇 |
1988年 | 12篇 |
1987年 | 9篇 |
1986年 | 11篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 11篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 6篇 |
1978年 | 4篇 |
1977年 | 6篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 4篇 |
排序方式: 共有4237条查询结果,搜索用时 15 毫秒
111.
Fressinaud Catherine Thomas Olivier Umerska Anita Monika Saulnier Patrick 《Neurochemical research》2020,45(11):2732-2748
Neurochemical Research - Promoting remyelination in multiple sclerosis is important to prevent axon degeneration, given the lack of curative treatment. Although some growth factors improve this... 相似文献
112.
Monika Chaudhary Neeraj Kumar Ashish Baldi Ramesh Chandra M. Arockia Babu 《Journal of biomolecular structure & dynamics》2020,38(1):200-218
AbstractWith an endeavor to develop novel curcumin analogs as potential anti-cancer agents, we designed and synthesized a series of Knoevenagel condensates by clubbing pyrazole carbaldehydes at the active methylene carbon atom of the curcumin backbone. Molecular docking studies were carried out to target the proposed derivatives on human kinase β (IKKβ), a potential anti-cancer target. The chloro derivative displayed five hydrogen bond interactions with a docking score of ?11.874?kcal/mol higher than curcumin (docking score =??7.434?kcal/mol). This was supported by the fact that the propellant shaped derivatives fitted aptly into the binding pocket. Molecular simulations studies were also conducted on the lead molecule and the results figured out that the stable complexes were developed as the minimal deviations per residue of protein within the range of 0.11–0.92 Å. The screened compounds were synthesized, characterized and evaluated in vitro for cytotoxicity against cervical cancer cell line, HeLa using standard cell proliferation assay. Chloro derivative and bromo analog demonstrated IC50 (half maximal inhibitory concentration) value of 14.2 and 18.6 µg/ml, respectively, significantly lower than 42.4 µg/ml of curcumin and higher than 0.008 µg/ml of paclitaxel. Induction of apoptosis was evaluated in the terms of cleavage of caspase-3 enzyme and they also exhibited 69.6 and 65.4% of apoptosis significantly higher than 19.9% induced by curcumin. In conclusion, chloro and bromo derivatives must be evaluated under a set of stringent in vitro and in vivo parameters for translating in to a clinically viable product.Communicated by Ramaswamy H. Sarma 相似文献
113.
Usha R. Dutta Vijaya Kumar Pidugu Ch. Venkateshwar Goud Christiane Hoefers Monika Hagemann Ashwin Dalal 《Gene》2013
Ambiguous genitalia or disorder of the sexual development is a birth defect where the external genitals do not have the typical appearance of either a male or female. Here we report a boy with ambiguous genitalia and short stature. The cytogenetic analysis by G-banding revealed a small Y chromosome and an additional material on the 15p arm. Further, molecular cytogenetic analysis by Fluorescence in situ hybridization (FISH) using whole chromosome paint probes showed the presence of Y sequences on the 15p arm, confirming that it is a Y;15 translocation. Subsequent, FISH with centromere probe Y showed two signals depicting the presence of two centromeres and differing with a balanced translocation. The dicentric nature of the derivative 15 chromosome was confirmed by FISH with both 15 and Y centromeric probes. Further, the delineation of the Y chromosomal DNA was also done by quantitative real time PCR. Additional Y-short tandem repeat typing was performed to find out the extent of deletion on small Y chromosome. Fine mapping was carried out with 8 Y specific BAC clones which helped in defining the breakpoint regions. MLPA was performed to check the presence or absence of subtelomeric regions and SHOX regions on Y. Finally array CGH helped us in confirming the breakpoint regions. In our study we identified and characterized a novel complex Y chromosomal rearrangement with a complete deletion of the Yq region and duplication of the Yp region with one copy being translocated onto the15p arm. This is the first report of novel and unique Y complex rearrangement showing a deletion, duplication and a translocation in the same patient. The possible mechanism of the rearrangement and the phenotype–genotype correlation are discussed. 相似文献
114.
Petra Mackeldanz Jürgen Alves Elisabeth Möncke-Buchner Karol H. Wyszomirski Detlev H. Krüger Monika Reuter 《Biochimie》2013
For efficient DNA hydrolysis, Type III restriction endonuclease EcoP15I interacts with two inversely oriented recognition sites in an ATP-dependent process. EcoP15I consists of two methylation (Mod) subunits and a single restriction (Res) subunit yielding a multifunctional enzyme complex able to methylate or to hydrolyse DNA. Comprehensive sequence alignments, limited proteolysis and mass spectroscopy suggested that the Res subunit is a fusion of a motor or translocase (Tr) domain of superfamily II helicases and an endonuclease domain with a catalytic PD…EXK motif. In the Tr domain, seven predicted helicase motifs (I, Ia, II–VI), a recently discovered Q-tip motif and three additional regions (IIIa, IVa, Va) conserved among Type III restriction enzymes have been identified that are predicted to be involved in DNA binding and ATP hydrolysis. Because DNA unwinding activity for EcoP15I (as for bona fide helicases) has never been found and EcoP15I ATPase rates are only low, the functional importance of the helicase motifs and regions was questionable and has never been probed systematically. Therefore, we mutated all helicase motifs and conserved regions predicted in Type III restriction enzyme EcoP15I and examined the functional consequences on EcoP15I enzyme activity and the structural integrity of the variants by CD spectroscopy. The resulting eleven enzyme variants all, except variant IVa, are properly folded showing the same secondary structure distribution as the wild-type enzyme. Classical helicase motifs I–VI are important for ATP and DNA cleavage by EcoP15I and mutations therein led to complete loss of ATPase and cleavage activity. Among the catalytically inactive enzyme variants three preserved the ability to bind ATP. In contrast, newly assigned motifs Q-tip, Ia and Va are not essential for EcoP15I activity and the corresponding enzyme variants were still catalytically active. DNA binding was only marginally reduced (2–7 fold) in all enzyme variants tested. 相似文献
115.
Yu Tong Elke Gabriel-Neumann Benard Ngwene Angelika Krumbein Susanne Baldermann Monika Schreiner Eckhard George 《Plant and Soil》2013,372(1-2):361-374
Aims
This study aimed to determine the effect of arbuscular mycorrhizal (AM) fungi and phosphorus (P) supply levels on β-carotene concentrations in sweet potato (Ipomoea batatas L.) tubers.Methods
Two commercial AM fungal isolates of Glomus intraradices (IFP Glintra) and Glomus mosseae (IFP Glm) which differ in their life cycles were used. Sweet potato plants were grown in a horizontal split-root system that consisted of two root compartments. A root-free fungal compartment that allowed the quantification of mycelial development was inserted into each root compartment. The two root compartments were inoculated either with the same or with different AM isolates, or remained free of mycorrhizal propagules. Each fungal treatment was carried out in two P supply levels.Results
In the low P supply level, mycorrhizal colonization significantly increased β-carotene concentrations in sweet potato tubers compared with the non-mycorrhizal plants. Glomus intraradices appeared to be more efficient in increasing β-carotene concentrations than G. mosseae. Dual inoculation of the root system with the two mycorrhizal fungi did not result in a higher increase in tuber β-carotene concentrations than inoculation with the single isolates. Improved P nutrition led to higher plant tuber biomass but was not associated with increased β-carotene concentrations.Conclusions
The results indicate a remarkable potential of mycorrhizal fungi to improve β-carotene concentrations in sweet potato tubers in low P fertilized soils. These results also suggest that β-carotene metabolism in sweet potato tubers might be specifically activated by root mycorrhizal colonization. 相似文献116.
Sorghum with its remarkable adaptability to drought and high temperature provides a model system for grass genomics and resource for gene discovery especially for abiotic stress tolerance. Group 3 LEA genes from barley and rice have been shown to play crucial role in abiotic stress tolerance. Here, we present a genome-wide analysis of LEA3 genes in sorghum. We identified four genes encoding LEA3 proteins in the sorghum genome and further classified them into LEA3A and LEA3B subgroups based on the conservation of LEA3 specific motifs. Further, expression pattern of these genes were analyzed in seeds during development and vegetative tissues under abiotic stresses. SbLEA3A group genes showed expression at early stage of seed development and increased significantly at maturity, while SbLEA3B group genes expressed only in matured seeds. Expression of SbLEA3 genes in response to abiotic stresses such as soil moisture deficit (drought), osmotic, salt, and temperature stresses, and exogenous ABA treatments was also studied in the leaves of 2-weeks-old seedlings. ABA and drought induced the expression of all LEA3 genes, while cold and heat stress induced none of them. Promoter analysis revealed the presence of multiple ABRE core cis-elements and a few low temperature response (LTRE)/drought responsive (DRE) cis-elements. This study suggests non-redundant function of LEA3 genes in seed development and stress tolerance in sorghum. 相似文献
117.
The Influence of Two Lithium Forms on the Growth, l-Ascorbic Acid Content and Lithium Accumulation in Lettuce Plants 总被引:1,自引:0,他引:1
Monika Kalinowska Barbara Hawrylak-Nowak Maria Szymańska 《Biological trace element research》2013,152(2):251-257
Lithium (Li) is a trace element that is essential in the human diet due to its importance for health and proper functioning of an organism. However, the biological activity of this metal in crop plants, which are the primary dietary sources of Li, is still poorly understood. The aim of the presented study was to comparatively analyse two Li chemical forms on the growth, as well as the l-ascorbic acid content, the Li accumulation and translocation in butterhead lettuce (Lactuca sativa L. var. capitata) cv. Justyna. The plants were grown in a nutrient solution enriched with Li in the form of LiCl or LiOH at the following concentrations: 0, 2.5, 20, 50 or 100 mg?Li?dm?3. The obtained results indicate that the presence of Li+ ions in the root environment reduced the yield of edible parts of the lettuce if the Li concentration in a nutrient solution had reached 20 mg?Li?dm?3. However, a yield reduction under these conditions was found to be significant only for LiOH. In plants exposed to 50 mg?Li?dm?3, both shoot and root fresh weights (FW) significantly decreased, regardless of the supplied Li chemical form. On the other hand, under the lowest LiOH dose, a significant increase in the root FW was noted, suggesting beneficial effects of Li on the growth of lettuce plants. However, applied Li concentrations and forms did not affect the l-ascorbic acid content in the lettuce leaves. Regardless of which Li form was used, Li accumulated mainly in the root tissues. An exception was the higher concentration of this metal in the shoots than in the roots of plants supplied with 100 mg?Li?dm?3 in LiCl, and there were almost the same Li concentrations in both examined organs of plants supplied with 100 mg?Li?dm?3 in LiOH. The effectiveness of Li translocation from roots to shoots rose with increasing Li concentrations in the growth medium, and this suggests a relatively ready translocation of this metal throughout the plant. Moreover, these results suggest that Li toxicity in lettuce plants is related to a high accumulation of this element in the root and shoot tissues, causing a drastic reduction in the yield, in the presence either of LiCl or LiOH, but not affecting the l-ascorbic acid accumulation in the leaves. 相似文献
118.
Joanna Suliburska Paweł Bogdański Monika Szulińska 《Biological trace element research》2013,151(2):263-268
The aim of this study was to assess the metabolic and physiological changes in rats fed a diet high in fat, fructose, and salt, and with excess iron level. Mineral status was also estimated. Wistar rats were assigned to groups fed either a standard control diet (C) or a diet high in fat, fructose, and salt. The noncontrol diets contained either normal (M) or high level (MFe) of iron. After 6 weeks, the length and weight of the rats were measured, and the animals were euthanized. The kidneys and gonads were collected, and blood samples were taken. Serum levels of insulin, nitric oxide, and iron were measured. The iron, zinc, copper, and calcium concentrations of tissues were determined. It was found that the M diet led to a significant increase in the relative kidney mass of the rats compared with the control group. Among the rats fed the M diet, markedly higher serum level of iron and lower levels of zinc and copper were observed in tissues, while significantly higher calcium levels were found in the gonads. The MFe diet resulted in decreased obesity index, insulin level, and nitric oxide serum concentration in the rats, when compared with both the M and C diets. The high iron level in the modified diet increased the relative mass of the gonads. The excess iron level in the diet disturbed the zinc, copper, and calcium status of tissues. The decrease in insulin and nitric oxide in rats fed the diet high in iron, fat, fructose, and salt was associated with disorders of zinc, copper, and calcium status, as well as with an increase in the relative mass of the gonads. 相似文献
119.
Sabina Gerber Christian Lizak Ga?lle Michaud Monika Bucher Tamis Darbre Markus Aebi Jean-Louis Reymond Kaspar P. Locher 《The Journal of biological chemistry》2013,288(13):8849-8861
N-Linked glycosylation is an essential post-translational protein modification in the eukaryotic cell. The initial transfer of an oligosaccharide from a lipid carrier onto asparagine residues within a consensus sequon is catalyzed by oligosaccharyltransferase (OST). The first X-ray structure of a complete bacterial OST enzyme, Campylobacter lari PglB, was recently determined. To understand the mechanism of PglB, we have quantified sequon binding and glycosylation turnover in vitro using purified enzyme and fluorescently labeled, synthetic peptide substrates. Using fluorescence anisotropy, we determined a dissociation constant of 1.0 μm and a strict requirement for divalent metal ions for consensus (DQNAT) sequon binding. Using in-gel fluorescence detection, we quantified exceedingly low glycosylation rates that remained undetected using in vivo assays. We found that an alanine in the −2 sequon position, converting the bacterial sequon to a eukaryotic one, resulted in strongly lowered sequon binding, with in vitro turnover reduced 50,000-fold. A threonine is preferred over serine in the +2 sequon position, reflected by a 4-fold higher affinity and a 1.2-fold higher glycosylation rate. The interaction of the +2 sequon position with PglB is modulated by isoleucine 572. Our study demonstrates an intricate interplay of peptide and metal binding as the first step of protein N-glycosylation. 相似文献
120.
Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders.