全文获取类型
收费全文 | 4418篇 |
免费 | 262篇 |
国内免费 | 2篇 |
出版年
2023年 | 20篇 |
2022年 | 53篇 |
2021年 | 99篇 |
2020年 | 59篇 |
2019年 | 72篇 |
2018年 | 101篇 |
2017年 | 93篇 |
2016年 | 134篇 |
2015年 | 217篇 |
2014年 | 198篇 |
2013年 | 287篇 |
2012年 | 343篇 |
2011年 | 363篇 |
2010年 | 250篇 |
2009年 | 342篇 |
2008年 | 249篇 |
2007年 | 244篇 |
2006年 | 207篇 |
2005年 | 207篇 |
2004年 | 175篇 |
2003年 | 181篇 |
2002年 | 147篇 |
2001年 | 45篇 |
2000年 | 65篇 |
1999年 | 38篇 |
1998年 | 36篇 |
1997年 | 31篇 |
1996年 | 23篇 |
1995年 | 25篇 |
1994年 | 25篇 |
1993年 | 33篇 |
1992年 | 17篇 |
1991年 | 10篇 |
1990年 | 18篇 |
1989年 | 14篇 |
1988年 | 12篇 |
1987年 | 11篇 |
1986年 | 18篇 |
1985年 | 15篇 |
1984年 | 16篇 |
1983年 | 11篇 |
1982年 | 17篇 |
1980年 | 13篇 |
1979年 | 10篇 |
1977年 | 8篇 |
1976年 | 10篇 |
1974年 | 16篇 |
1973年 | 14篇 |
1972年 | 7篇 |
1966年 | 10篇 |
排序方式: 共有4682条查询结果,搜索用时 15 毫秒
991.
By M. C. Deval T. Bök C. Ate T. Ulutürk Z. Tosunolu 《Zeitschrift fur angewandte Ichthyologie》2009,25(4):372-380
The aim of this study was to compare selectivity results of currently used 44 mm nominal polyamide (PA) diamond mesh- and alternatively suggested 40 mm nominal polyethylene (PE) square mesh- codends in the deepwater crustacean trawl fishery in the Antalya Bay, eastern Mediterranean. Selectivity experiments were carried out during targeted trawling of four commonly harvested crustacean species: giant red shrimp Aristaeomorpha foliacea , 'blue and red' shrimp Aristeus antennatus , rose shrimp Parapenaeus longirostris , and pandalid shrimp Plesionika martia . A conventional bottom trawl of 600 meshes around the fishing circle was operated onboard a commercial stern trawler between 6 and 18 June 2007. Depth of the fishing area varied between 441 and 630 m. Data were collected using the covered codend technique, and analyzed using a logistic equation with maximum likelihood for individual and pooled hauls. The commercially used trawl codend was unable to release immature crustaceans. Selectivity parameters of the three species of crustaceans were distinctly lower when collected with the polyamide diamond mesh than with the polyethylene square mesh, except in the case of giant red shrimp for which values were similar. However, the present and previous results show that in square mesh codends, mesh sizes must be more than 40 mm in order to keep catches clear of specimens below minimum landing sizes or 50% sexual maturity sizes of crustaceans in the Mediterranean. This study suggests that regulating mesh size by requiring square mesh openings during deep water crustacean trawling of the eastern Mediterranean is essential for the release of immature individuals. 相似文献
992.
Maria Helena Vianna Metello Jacob Daiane da R. Janner Matheus Parmegiani Jahn Luiz Carlos Kucharski Adriane Belló‐Klein Maria Flavia Marques Ribeiro 《Cell biochemistry and function》2010,28(1):52-57
Ageing is an inevitable biological process characterized by a general decline in various physiological functions. DHEA and DHEAS levels are maximal between the second and third life decades, then start to decline 2% per year, leaving a residual of 10–20% of the peak production by the eighth decade. Erythrocytes are exposed to frequent oxidative stress due to the oxygen radicals continuously generated by haemoglobin auto‐oxidation. We investigated DHEA chronic (10 mg/kg, subcutaneously, for 5 weeks) effects over oxidative stress markers in erythrocytes of male Wistar rats of 3, 13 and 18 month‐old. In the 13 month‐old group, we found increased lipid peroxidation (LPO), superoxide dismutase (SOD), glutathione‐S‐transferase and catalase activities when compared to the other age groups. DHEA produced a marked increase in LPO of 13 month‐old group when compared to its control. DHEA exerted this pro‐oxidant effects in all ages studied, especially in age 13 month‐old. It seems that at 13 month‐old there would be an important depletion of some specific anti‐oxidant in order to determine such susceptibility to DHEA effects. Since this approach allows a minimally invasive assessment, it would be useful as a routine method in human clinical studies investigating DHEA effects during the ageing process. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
993.
THE EFFECTS OF SODIUM CHLORIDE ON HIGHER PLANTS 总被引:6,自引:0,他引:6
(1) This review concentrates on the effect of sodium chloride on the growth of higher plants, being primarily concerned with relatively high concentrations i.e. 50 mmol 1-1 and above, though something is also said about those instances when sodium acts as a micronutrient. Emphasis is placed on particular species or genera for which enough information is available to discuss possible mechanisms. (2) Trace amounts of sodium are required for the growth of plants using the C4 pathway of carbon fixation and may also be important in plants with Crassulacean acid metabolism. (3) The increased growth of Beta vulgaris brought about by sodium chloride can in part be explained by a sparing effect on potassium. However, growth is still increased when sufficient potassium is available. Complementary studies with rubidium indicate that the hormone balance in the plant may be changed. Sodium chloride also increases the level of sucrose in storage roots and allows beet plants to withstand water stress more readily, possibly by increased turgor pressure. (4) Sodium chloride increases production of dry matter in C4 species of Atriplex under conditions of low relative humidity because water loss is reduced and photo-synthesis hardly affected. (5) Succulence in many plants is stimulated by salinity. The essential basis of the phenomenon is an increased water potential gradient between the leaf and the external medium. In some instances, it is the accumulation of chloride which is important; in others it is the accumulation of cations, when potassium can be as effective as sodium. (6) Salinity reduces the final area achieved by growing leaves. Most of the studies have been made on Phaseolus vulgaris and an important early event is the reduction in the rate of expansion of the epidermal cells and this may be accompanied by a decrease in their number. Reduction of epidermal cell size is a result of water stress; sodium chloride may directly affect cell division, though water stress cannot be ruled out. Whether salinity brings about inhibition of cell division depends upon the calcium content of the medium – a high content is accompanied solely by a reduction in epidermal cell size. (7) Hormones, as yet unspecified, may play an important part in response of a growing leaf to salinity. However, there is no evidence that sodium chloride per se has an effect on hormone balance within the plant. So far, any measured changes in levels of specific hormones can be ascribed to the osmotic effects of the saline medium. (8) Two estimates by flux analysis of cytoplasmic concentration of sodium in plants growing in conditions of high salinity give a value of around 150 mmol 1-1. There is no similar information for chloride. Other techniques (histochemistry and X-ray micro-probe analysis) give questionable information. (9) There is now extensive information to show that enzymes of halophytes (other than ATPases) do not differ significantly from those of other higher plants with respect to their sensitivity in vitro to sodium chloride. There is a need for further work with respect to the activity of enzymes in the presence of those metabolites which have the highest cytoplasmic concentration. (10) Sodium-stimulated ATPases have been isolated from plant cells but their distribution amongst higher plants is restricted. (11) There are a number of reports of changed metabolism brought about by saline treatments but it is not clear how far the effects of sodium chloride and water stress are confounded. (12) Sodium appears to increase the sucrose levels in sugar beet by an inhibitory effect on product starch-granule-bound ADP-glucose starch synthase. (13) Reversal of a sodium pump located at the plasmalemma might have an effect on cell turgor. (14) Sodium (like other monovalent cations) causes loss of materials from plant cells, possibly through an effect on carrier proteins; calcium prevents this from happening. Calcium also allows plants to grow better in saline conditions by a depression of sodium uptake by and transport within the plant. The properties and composition of the membranes of mesophytes and halophytes need to be compared. (15) A saline medium exerts a major effect on plant growth through water stress to which a halophyte must adapt. As well as this, the cytoplasmic concentration of sodium chloride must be kept lower than the total cellular concentration of the salt. Unless this happens, it is likely that enzymic activity will be reduced due, in some instances, to an unspecific effect of a high concentration of monovalent cations and/or chloride and in other instances to competition between sodium and other cations, specifically potassium, for activation sites on enzymes, e.g. pyruvate kinase. (16) Further work is required to separate the osmotic effects from the specific effect of sodium chloride after it has entered the plant. As well as this, it has become clear that more information is needed about the mineral nutrition of halophytes. 相似文献
994.
The N7 of purine nucleotides presents one of the most dominant metal ion binding sites in nucleic acids. However, the interactions between kinetically labile metal ions like Mg2+ and these nitrogen atoms are inherently difficult to observe in large RNAs. Rather than using the insensitive direct 15N detection, here we have used 2J-[1H,15N]-HSQC (Heteronuclear Single Quantum Coherence) NMR experiments as a fast and efficient method to specifically observe and characterize such interactions within larger RNA constructs. Using the 27 nucleotides long branch domain of the yeast-mitochondrial group II intron ribozyme Sc.ai5γ as an example, we show that direct N7 coordination of a Mg2+ ion takes place in a tetraloop nucleotide. A second Mg2+ ion, located in the major groove at the catalytic branch site, coordinates mainly in an outer-sphere fashion to the highly conserved flanking GU wobble pairs but not to N7 of the sandwiched branch adenosine. 相似文献
995.
Andrei Sakai Ana Paula de Sousa Mesquita Erica Valadares de Castro Levatti Anita Hilda Straus Helena B. Nader Carla Cristina Lopes Luciano Caseli 《生物化学与生物物理学报:生物膜》2019,1861(10):182992
Trastuzumab (Tmab) is a monoclonal antibody administered as targeted therapy for HER2-positive breast cancer whose molecular interactions at the HER2 receptor microenvironment are not completely clarified yet. This paper describes the influence of Tmab in the molecular organization of films of biological-relevant molecules at the air water interface. For that, we spread components of tumorigenic and non-tumorigenic cells directly on the air-water interface. The physicochemical properties of the films were investigated with surface pressure-area isotherms and Brewster angle microscopy, and distinction between the cellular lines with higher or lower amount of HER2 could be detected based on the physicochemical properties of the interfacial films. The systems organized at the air-water interface were transferred to solid supports as Langmuir-Blodgett films and the nano-scale morphology investigated with atomic force microscopy. The overall results related to Tmab interacting with the films lead to the conclusion that Tmab tends to condense rich-HER2 films, causing irregular dimerization of the receptor protein, changing the membrane topography of the films, with formation of phases with different levels of reflectivity and aggregation morphology, and finally revealing that the interaction of the antibody with proteo-lipidic biointerfaces is modulated by the film composition. We believe that novel perspectives concerning the molecular interactions in the plasma membrane microenvironment through Langmuir monolayers can be obtained from this work in order to enhance the Tmab-based cancer therapy. 相似文献
996.
997.
Anja Meissner Helena I. Boshoff Mahalakshmi Vasan Benjamin P. Duckworth Clifton E. Barry Courtney C. Aldrich 《Bioorganic & medicinal chemistry》2013,21(21):6385-6397
A series of 2-aminothiazoles was synthesized based on a HTS scaffold from a whole-cell screen against Mycobacterium tuberculosis (Mtb). The SAR shows the central thiazole moiety and the 2-pyridyl moiety at C-4 of the thiazole are intolerant to modification. However, the N-2 position of the aminothiazole exhibits high flexibility and we successfully improved the antitubercular activity of the initial hit by more than 128-fold through introduction of substituted benzoyl groups at this position. N-(3-Chlorobenzoyl)-4-(2-pyridinyl)-1,3-thiazol-2-amine (55) emerged as one of the most promising analogues with a MIC of 0.024 μM or 0.008 μg/mL in 7H9 media and therapeutic index of nearly ~300. However, 55 is rapidly metabolized by human liver microsomes (t1/2 = 28 min) with metabolism occurring at the invariant aminothiazole moiety and Mtb develops spontaneous low-level resistance with a frequency of ~10?5. 相似文献
998.
Mozaniel Santana de Oliveira Valdeline Maria Pereira da Silva Lucas Cantão Freitas Sebastião Gomes Silva Jorddy Nevez Cruz Eloisa Helena de Aguiar Andrade 《化学与生物多样性》2021,18(4):e2000982
Bignonia nocturna (Bignoniaceae) is a plant used for medicinal purposes by the Amazonian indigenous peoples. To date, there have been no reported studies on its toxicity. The present study aimed to evaluate the chemical composition of essential oils obtained from Bignonia nocturna by different extraction techniques. In addition, an in silico study of the molecular interactions was performed using molecular docking and molecular dynamics. The extractions were carried out by hydrodistillation, simultaneous distillation-extraction, and steam distillation, using samples collected from the Amazon in summer and winter. The chemical composition was analyzed by GC/FID and GC/MS, and the cytotoxic activity in Artemia salina Leach was evaluated. The maximum yield (1.38 % w/w) was obtained by hydrodistillation. The results indicated that benzaldehyde predominated in all the fractions of both the volatile concentrate and the essential oils. In addition, the oil proved to be highly toxic to Artemia salina. The computer simulation results indicated that benzaldehyde strongly interacts with acetylcholinesterase, which is the likely interaction mechanism responsible for the cytotoxicity. 相似文献
999.
Antonia Janssen Sebastian Fiebiger Helena Bros Laura Hertwig Silvina Romero-Suarez Isabell Hamann Coralie Chanvillard Judith Bellmann-Strobl Friedemann Paul Jason M. Millward Carmen Infante-Duarte 《PloS one》2015,10(6)
We previously demonstrated that epigallocatechin-3-gallate (EGCG) synergizes with the immunomodulatory agent glatiramer acetate (GA) in eliciting anti-inflammatory and neuroprotective effects in the relapsing-remitting EAE model. Thus, we hypothesized that mice with chronic EAE may also benefit from this combination therapy. We first assessed how a treatment with a single dose of GA together with daily application of EGCG may modulate EAE. Although single therapies with a suboptimal dose of GA or EGCG led to disease amelioration and reduced CNS inflammation, the combination therapy had no effects. While EGCG appeared to preserve axons and myelin, the single GA dose did not improve axonal damage or demyelination. Interestingly, the neuroprotective effect of EGCG was abolished when GA was applied in combination. To elucidate how a single dose of GA may interfere with EGCG, we focused on the anti-inflammatory, iron chelating and anti-oxidant properties of EGCG. Surprisingly, we observed that while EGCG induced a downregulation of the gene expression of heme oxygenase-1 (HO-1) in affected CNS areas, the combined therapy of GA+EGCG seems to promote an increased HO-1 expression. These data suggest that upregulation of HO-1 may contribute to diminish the neuroprotective benefits of EGCG alone in this EAE model. Altogether, our data indicate that neuroprotection by EGCG in chronic EAE may involve regulation of oxidative processes, including downmodulation of HO-1. Further investigation of the re-dox balance in chronic neuroinflammation and in particular functional studies on HO-1 are warranted to understand its role in disease progression. 相似文献
1000.