全文获取类型
收费全文 | 9781篇 |
免费 | 687篇 |
国内免费 | 2篇 |
出版年
2023年 | 73篇 |
2022年 | 47篇 |
2021年 | 123篇 |
2020年 | 107篇 |
2019年 | 93篇 |
2018年 | 263篇 |
2017年 | 260篇 |
2016年 | 375篇 |
2015年 | 537篇 |
2014年 | 512篇 |
2013年 | 648篇 |
2012年 | 888篇 |
2011年 | 746篇 |
2010年 | 509篇 |
2009年 | 355篇 |
2008年 | 591篇 |
2007年 | 631篇 |
2006年 | 580篇 |
2005年 | 510篇 |
2004年 | 508篇 |
2003年 | 406篇 |
2002年 | 416篇 |
2001年 | 107篇 |
2000年 | 90篇 |
1999年 | 63篇 |
1998年 | 60篇 |
1997年 | 38篇 |
1996年 | 44篇 |
1995年 | 53篇 |
1994年 | 36篇 |
1993年 | 37篇 |
1992年 | 49篇 |
1991年 | 53篇 |
1990年 | 36篇 |
1989年 | 28篇 |
1988年 | 33篇 |
1986年 | 26篇 |
1985年 | 41篇 |
1984年 | 39篇 |
1983年 | 48篇 |
1982年 | 36篇 |
1981年 | 29篇 |
1980年 | 23篇 |
1979年 | 27篇 |
1978年 | 23篇 |
1977年 | 20篇 |
1976年 | 42篇 |
1975年 | 28篇 |
1974年 | 21篇 |
1973年 | 25篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
881.
We investigated the changes of water level and vegetation in a restored cut-over raised bog in response to a hydrological
protection zone established around the bog. The restoration began 1997 and techniques involved ditch blocking within and around
the bog to stimulate a return to conditions of intact bog ecosystems. In order to monitor the rehabilitation of the raised
bog, water levels and vegetation have been recorded since before restoration measures began. The monitoring is ongoing, but
an assessment of 15 year’s data (1994–2008) is presented. A hydrological protection zone with continuous high water levels
could be established around the raised bog which minimizes the runoff of precipitation. Shortly after the first measures,
the water levels increased significantly at all dipwells. Parallel to the increasing water levels a vascular plant species
assemblage and a diverse Sphagnum community developed. In particular Sphagnum fimbriatum, S. palustre, S. recurvum and S. squarrosum spread efficiently. The cover of trees decreased significantly because of high water levels and ongoing acidification by
Sphagnum spp. The high water levels have stimulated the re-vegetation and the hydrology self-regulation of the acrotelm. The successful
regeneration of the acrotelm particularly became apparent in years with below-average precipitations (e.g. 2008), when the
water levels in the central parts of the raised bog did not fall back to the low level reached in previous years, which had
also remarkably water deficits (e.g. 2003). 相似文献
882.
Scarlet Nere Ortega Marcia Nitschke Ana Maria Mouad Maria Diva Landgraf Maria Olímpia Oliveira Rezende Mirna Helena Regali Seleghim Lara Durães Sette André Luiz Meleiro Porto 《Biodegradation》2011,22(1):43-50
The fungi Aspergillus sydowii Ce15, Aspergillus sydowii Ce19, Aspergillus sydowii Gc12, Bionectria sp. Ce5, Penicillium miczynskii Gc5, Penicillium raistrickii Ce16 and Trichoderma sp. Gc1, isolated from marine sponges Geodia corticostylifera and Chelonaplysylla erecta, were evaluated for their ability to grow in the presence of DDD pesticide. Increasing concentrations of DDD pesticide, i.e.,
5.0 mg (1.56 × 10−12 mmol), 10.0 mg (3.12 × 10−2 mmol) and 15.0 mg (4.68 × 10−2 mmol) in solid and liquid culture media were tested. The fungi Trichoderma sp. Gc1 and Penicillium miczynskii Gc5 were able to grow in the presence of up to 15.0 mg of DDD, suggesting their potential for biodegradation. A 100% degradation
of DDD was attained in liquid culture medium when Trichoderma sp. Gc1 was previously cultivated for 5 days and supplemented with 5.0 mg of DDD in the presence of hydrogen peroxide. However,
the quantitative analysis showed that DDD was accumulated on mycelium and biodegradation level reached a maximum value of
58% after 14 days. 相似文献
883.
Rossi FR Gárriz A Marina M Romero FM Gonzalez ME Collado IG Pieckenstain FL 《Molecular plant-microbe interactions : MPMI》2011,24(8):888-896
Botrytis cinerea, as a necrotrophic fungus, kills host tissues and feeds on the remains. This fungus is able to induce the hypersensitive response (HR) on its hosts, thus taking advantage on the host's defense machinery for generating necrotic tissues. However, the identity of HR effectors produced by B. cinerea is not clear. The aim of this work was to determine whether botrydial, a phytotoxic sesquiterpene produced by B. cinerea, is able to induce the HR on plant hosts, using Arabidopsis thaliana as a model. Botrydial induced the expression of the HR marker HSR3, callose deposition, and the accumulation of reactive oxygen species and phenolic compounds. Botrydial also induced the expression of PR1 and PDF1.2, two pathogenesis-related proteins involved in defense responses regulated by salicylic acid (SA) and jasmonic acid (JA), respectively. A. thaliana and tobacco plants defective in SA signaling were more resistant to botrydial than wild-type plants, as opposed to A. thaliana plants defective in JA signaling, which were more sensitive. It can be concluded that botrydial induces the HR on its hosts and its effects are modulated by host signaling pathways mediated by SA and JA. 相似文献
884.
Cruces-Ángeles ME Cabrera N Pérez-Montfort R Reyes-López CA Hernández-Arana A 《Protein and peptide letters》2011,18(12):1290-1298
Several variants of Saccharomyces cerevisiae triosephosphate isomerase (yTIM) were studied to determine how mutations of conserved and non-conserved Cys residues affect the enzyme. Wild-type yTIM has two buried free cysteines: Cys 41 (non-conserved) and the invariant Cys 126. Single-site mutants, containing substitutions of these cysteines with Ala, Val, or Ser (the three most conservative changes for a buried Cys, according to substitution matrices), were examined for stability and enzymatic activity. Neither of the Cys residues was found to be essential for enzyme catalysis. Determination of the global stability of the mutants indicated that, regardless of which Cys was substituted, individual Cys→Ala and Cys→Val mutations, as well as the C41S substitution, all decrease the unfolding free energy of the dimeric protein by less than 23 kJ mol(-1) (at 37 °C, pH 7.4), as compared to the wild-type enzyme. In contrast, a substantially larger destabilization (37 kJ mol(-1)) was found in the C126S mutant. These results suggest that, with the exception of C126S, all of these mutations can be regarded as neutral (i.e., mutations that do not impair the reproductive success of the organism). Accordingly, Cys 126 has remained invariant across evolution because its neutral substitutions by Ala or Val would require a highly unlikely, concerted double mutation at any of the Cys codons. Furthermore, detrimental effects to a cell expressing the C126S TIM mutant more likely arise from the high unfolding rate of this enzyme. 相似文献
885.
Cuperus R van Kuilenburg AB Leen R Bras J Caron HN Tytgat GA 《Free radical biology & medicine》2011,51(6):1213-1220
To enhance the efficacy of fenretinide (4HPR)-induced reactive oxygen species (ROS) in neuroblastoma, 4HPR was combined with buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, in neuroblastoma cell lines and spheroids, the latter being a three-dimensional tumor model. 4HPR exposure (2.5-10 μM, 24 h) resulted in ROS induction (114-633%) and increased GSH levels (68-120%). A GSH depletion of 80% of basal levels was observed in the presence of BSO (25-100 μM, 24 h). The 4HPR-BSO combination resulted in slightly increased ROS levels (1.1- to 1.3-fold) accompanied by an increase in cytotoxicity (110-150%) compared to 4HPR treatment alone. A correlation was observed between the ROS-inducing capacity of each cell line and the increase in cytotoxicity induced by 4HPR-BSO compared to 4HPR. No significant correlation between baseline antioxidant levels and sensitivity to 4HPR or BSO was observed. In spheroids, 4HPR-BSO induced a strong synergistic growth retardation and induction of apoptosis. Our data show that BSO increased the cytotoxic effects of 4HPR in neuroblastoma monolayers and spheroids in ROS-producing cell lines. This indicates that the 4HPR-BSO combination might be a promising new strategy in the treatment of neuroblastoma. 相似文献
886.
887.
Expression of functional recombinant human growth hormone in transgenic soybean seeds 总被引:1,自引:0,他引:1
Cunha NB Murad AM Cipriano TM Araújo AC Aragão FJ Leite A Vianna GR McPhee TR Souza GH Waters MJ Rech EL 《Transgenic research》2011,20(4):811-826
We produced human growth hormone (hGH), a protein that stimulates growth and cell reproduction, in genetically engineered soybean [Glycine max (L.) Merrill] seeds. Utilising the alpha prime (α') subunit of β-conglycinin tissue-specific promoter from soybean and the α-Coixin signal peptide from Coix lacryma-jobi, we obtained transgenic soybean lines that expressed the mature form of hGH in their seeds. Expression levels of bioactive hGH up to 2.9% of the total soluble seed protein content (corresponding to approximately 9?g?kg(-1)) were measured in mature dry soybean seeds. The results of ultrastructural immunocytochemistry assays indicated that the recombinant hGH in seed cotyledonary cells was efficiently directed to protein storage vacuoles. Specific bioassays demonstrated that the hGH expressed in the soybean seeds was fully active. The recombinant hGH protein sequence was confirmed by mass spectrometry characterisation. These results demonstrate that the utilisation of tissue-specific regulatory sequences is an attractive and viable option for achieving high-yield production of recombinant proteins in stable transgenic soybean seeds. 相似文献
888.
Maisuria BB Actis ML Hardrict SN Falkinham JO Cole MF Cihlar RL Peters SM Macri RV Sugandhi EW Williams AA Poppe MA Esker AR Gandour RD 《Bioorganic & medicinal chemistry》2011,19(9):2918-2926
Homologous dicarboxyl dendritic amphiphiles-RCONHC(CH(3))(CH(2)CH(2)COOH)(2), 4(n); and ROCONHC(CH(3))(CH(2)CH(2)COOH)(2), 5(n), where R=n-C(n)H(2)(n)(+1) and n=13-22 carbon atoms-were synthesized. Critical micelle concentrations (CMCs) in aqueous triethanolamine solutions and at pH 7.4 were measured along with hemolytic activity (effective concentrations, EC(10)) in phosphate-buffered saline (PBS). LogCMC showed a linear dependence on chain length (n); the longest chain in each series had the lowest CMC-in triethanolamine: 4(21), 180μM and 5(22), 74μM and at pH 7.4: 4(21), 78μM and 5(22), 33μM. These two series, 4(n) and 5(n), and three series of homologous tricarboxyl dendritic amphiphiles-RCONHC(CH(2)CH(2)COOH)(3), 1(n); ROCONHC(CH(2)CH(2)COOH)(3), 2(n); RNHCONHC(CH(2)CH(2)COOH)(3), 3(n), where R=n-C(n)H(2)(n)(+1) and n=13-22 carbon atoms-were tested for growth inhibition of Staphylococcus aureus strain ATCC 6358 and methicillin-resistant S. aureus (MRSA) strain ATCC 43330 by microdilution in 0.1-strength brain heart infusion broth (BHIB). Amphiphiles 4(19), 4(21), 5(18), and 5(20) showed the strongest antibacterial activity (2.2-3.4μg/mL) against S. aureus (vancomycin, MIC=0.25μg/mL). These four plus 1(21), 2(20), 2(22), and 3(20) exhibited the strongest antibacterial activity (1.7-6.8μg/mL) against MRSA (vancomycin, MIC=0.25μg/mL). The MICs of these amphiphiles against six clinical MRSA were similar to those against the ATCC strain. In PBS, EC(10)s of the most active homologues ranged from 7 to 18μg/mL and 18 to 220μg/mL for di- and tricarboxyl dendritic amphiphiles, respectively. To assess the potential safety of using dendritic amphiphiles as drugs, measurements of micellar and hemolytic properties were conducted in the same medium (full-strength BHIB) that was used for antibacterial activity. The CMCs (9-36μg/mL, ~18-72μM) of ten amphiphiles were measured by microdilution (log2 progression) with dye-covered beads. The EC(10)s were similar to those in PBS. The MICs of most amphiphiles (14-72μg/mL) and vancomycin (1.1-2.2μg/mL) against both S. aureus and MRSA increased significantly compared to the MICs measured in 0.1-strength BHIB. The one exception, 5(18), had an MIC against S. aureus of 1.1μg/mL compared to vancomycin (2.2μg/mL). With CMC (9-18μg/mL) and EC(10) (16μg/mL) values higher than the MIC, 5(18) was discovered as a lead for further development. 相似文献
889.
Pevet I Brulé C Tizot A Gohier A Cruzalegui F Boutin JA Goldstein S 《Bioorganic & medicinal chemistry》2011,19(8):2517-2528
Among the recently investigated targets for cancer therapy is the c-Src non-receptor tyrosine kinase. Indeed research around deregulated activity of this enzyme has proven its role in tumor progression, while the beneficial effects of c-Src inhibitors in several pathological models has also been demonstrated. We report here the preparation and pharmacological profile of a novel series of c-Src inhibitors that was elaborated around a 3-amino-thieno[2,3-b]pyridine discovered during an HTS campaign. c-Src enzyme inhibition and c-Src inhibition were investigated in a series of related compounds derived from the initial hit. Molecular modeling as well as X-ray studies on one active compound allowed us to hypothesize on ligand orientation and interactions within the ATP hydrophobic pocket. Design and synthesis of structural analogs then led to new ligands possessing quite efficient enzymatic and c-Src inhibition. The structure-activity elements disclosed in this study shed light on the role played by substituents on the thienopyridine ring as well as the impact of other aromatic moieties in the molecule when interacting with the enzyme. 相似文献
890.