全文获取类型
收费全文 | 3603篇 |
免费 | 239篇 |
国内免费 | 2篇 |
出版年
2023年 | 22篇 |
2022年 | 40篇 |
2021年 | 87篇 |
2020年 | 60篇 |
2019年 | 82篇 |
2018年 | 106篇 |
2017年 | 91篇 |
2016年 | 128篇 |
2015年 | 180篇 |
2014年 | 162篇 |
2013年 | 237篇 |
2012年 | 225篇 |
2011年 | 226篇 |
2010年 | 157篇 |
2009年 | 145篇 |
2008年 | 170篇 |
2007年 | 151篇 |
2006年 | 164篇 |
2005年 | 127篇 |
2004年 | 137篇 |
2003年 | 108篇 |
2002年 | 112篇 |
2001年 | 85篇 |
2000年 | 77篇 |
1999年 | 75篇 |
1998年 | 29篇 |
1997年 | 30篇 |
1996年 | 24篇 |
1995年 | 37篇 |
1994年 | 22篇 |
1993年 | 24篇 |
1992年 | 38篇 |
1991年 | 42篇 |
1990年 | 34篇 |
1989年 | 37篇 |
1988年 | 32篇 |
1987年 | 33篇 |
1986年 | 38篇 |
1985年 | 25篇 |
1984年 | 14篇 |
1981年 | 14篇 |
1979年 | 18篇 |
1978年 | 15篇 |
1977年 | 16篇 |
1975年 | 16篇 |
1974年 | 23篇 |
1973年 | 17篇 |
1971年 | 11篇 |
1969年 | 13篇 |
1968年 | 14篇 |
排序方式: 共有3844条查询结果,搜索用时 672 毫秒
951.
H. Faneca Isabel Tomaz Gisela Gonçalves M.C. Pedroso de Lima João Costa Pessoa M. Margarida C.A. Castro 《Journal of inorganic biochemistry》2009,103(4):601-608
The behaviour of three vanadium(V) systems, namely the pyridinone (VV-dmpp), the salicylaldehyde (VV-salDPA) and the pyrimidinone (VV-MHCPE) complexes, is studied in aqueous solutions, under aerobic and physiological conditions using 51V NMR, EPR and UV-Visible (UV-Vis) spectroscopies. The speciations for the VV-dmpp and VV-salDPA have been previously reported. In this work, the system VV-MHCPE is studied by pH-potentiometry and 51V NMR. The results indicate that, at pH ca. 7, the main species present are (VVO2)L2 and (VVO2)LH−1 (L = MHCPE−) and hydrolysis products, similar to those observed in aqueous solutions of VV-dmpp. The latter species is protonated as the pH decreases, originating (VVO2)L and (VVO2)LH. All the VV-species studied are stable in aqueous media with different compositions and at physiological pH, including the cell culture medium. The compounds were screened for their potential cytotoxic activity in two different cell lines. The toxic effects were found to be incubation time and concentration dependent and specific for each compound and type of cells. The HeLa tumor cells seem to be more sensitive to drug effects than the 3T3-L1 fibroblasts. According to the IC50 values and the results on reversibility to drug effects, the VV-species resulting from the VV-MHCPE system show higher toxicity in the tumor cells than in non-tumor cells, which may indicate potential antitumor activity. 相似文献
952.
Alessandra de Santana Braga Barbosa Ribeiro Cláudio Carlos da Silva Flávia de Castro Pereira Aliny Pereira de Lima Cesar Augusto Sam Tiago Vilanova-Costa Simone Santos Aguiar Luiz Alfredo Pavanin Aparecido Divino da Cruz Elisângela de Paula Silveira-Lacerda 《Biological trace element research》2009,130(3):249-261
Chemotherapeutic agents play an important role in cancer treatment mostly due their systemic action on human organism allowing
access to liquid tumors and even metastases. Among these drugs, ruthenium compounds have been showing promising results to
treat tumors and represent an important development of new antitumor therapy. This study presents the evaluation of cis-(dichloro)tetraammineruthenium(III) chloride, cis-[RuCl2(NH3)4]Cl, genotoxic effects using human peripheral blood lymphocytes cultured in vitro. Mitotic index (MI), chromosome aberrations
(CA), and DNA damage using the comet assay were analyzed. MI in human peripheral blood lymphocyte cultures treated with 1,
10, 100, and 1,000 μg mL−1
cis-[RuCl2(NH3)4]Cl were 5.9%, 4.6%, 3.9%, and 0%, respectively. Doxorubicin chloridate was used as the positive control. CA derived from
1, 10, and 100 μg mL−1 concentrations were defined as spontaneous when compared with the negative control, and at the concentration of 1,000 μg
mL−1, the cell cycle was inhibited (IM = 0%). Results obtained for the comet assay using cis-[RuCl2(NH3)4]Cl suggest that this compound has no genotoxic activity against cultured human peripheral blood lymphocytes. 相似文献
953.
Angelo Gámez-Pozo Iker Sánchez-Navarro Manuel Nistal Enrique Calvo Rosario Madero Esther Díaz Emilio Camafeita Javier de Castro Juan Antonio López Manuel González-Barón Enrique Espinosa Juan ángel Fresno Vara 《PloS one》2009,4(11)
Background
Proteomics is expected to play a key role in cancer biomarker discovery. Although it has become feasible to rapidly analyze proteins from crude cell extracts using mass spectrometry, complex sample composition hampers this type of measurement. Therefore, for effective proteome analysis, it becomes critical to enrich samples for the analytes of interest. Despite that one-third of the proteins in eukaryotic cells are thought to be phosphorylated at some point in their life cycle, only a low percentage of intracellular proteins is phosphorylated at a given time.Methodology/Principal Findings
In this work, we have applied chromatographic phosphopeptide enrichment techniques to reduce the complexity of human clinical samples. A novel method for high-throughput peptide profiling of human tumor samples, using Parallel IMAC and MALDI-TOF MS, is described. We have applied this methodology to analyze human normal and cancer lung samples in the search for new biomarkers. Using a highly reproducible spectral processing algorithm to produce peptide mass profiles with minimal variability across the samples, lineal discriminant-based and decision tree–based classification models were generated. These models can distinguish normal from tumor samples, as well as differentiate the various non–small cell lung cancer histological subtypes.Conclusions/Significance
A novel, optimized sample preparation method and a careful data acquisition strategy is described for high-throughput peptide profiling of small amounts of human normal lung and lung cancer samples. We show that the appropriate combination of peptide expression values is able to discriminate normal lung from non-small cell lung cancer samples and among different histological subtypes. Our study does emphasize the great potential of proteomics in the molecular characterization of cancer. 相似文献954.
Background
The loss of photosynthesis has occurred often in eukaryotic evolution, even more than its acquisition, which occurred at least nine times independently and which generated the evolution of the supergroups Archaeplastida, Rhizaria, Chromalveolata and Excavata. This secondary loss of autotrophic capability is essential to explain the evolution of eukaryotes and the high diversity of protists, which has been severely underestimated until recently. However, the ecological and evolutionary scenarios behind this evolutionary “step back” are still largely unknown.Methodology/Principal Findings
Using a dynamic model of heterotrophic and mixotrophic flagellates and two types of prey, large bacteria and ultramicrobacteria, we examine the influence of DOC concentration, mixotroph''s photosynthetic growth rate, and external limitations of photosynthesis on the coexistence of both types of flagellates. Our key premises are: large bacteria grow faster than small ones at high DOC concentrations, and vice versa; and heterotrophic flagellates are more efficient than the mixotrophs grazing small bacteria (both empirically supported). We show that differential efficiency in bacteria grazing, which strongly depends on cell size, is a key factor to explain the loss of photosynthesis in mixotrophs (which combine photosynthesis and bacterivory) leading to purely heterotrophic lineages. Further, we show in what conditions an heterotroph mutant can coexist, or even out-compete, its mixotrophic ancestor, suggesting that bacterivory and cell size reduction may have been major triggers for the diversification of eukaryotes.Conclusions/Significance
Our results suggest that, provided the mixotroph''s photosynthetic advantage is not too large, the (small) heterotroph will also dominate in nutrient-poor environments and will readily invade a community of mixotrophs and bacteria, due to its higher efficiency exploiting the ultramicrobacteria. As carbon-limited conditions were presumably widespread throughout Earth history, such a scenario may explain the numerous transitions from phototrophy to mixotrophy and further to heterotrophy within virtually all major algal lineages. We challenge prevailing concepts that affiliated the evolution of phagotrophy with eutrophic or strongly light-limited environments only. 相似文献955.
Carlos Gustavo Vasconcelos de Moraes Alexandre Soares Castro Reis Milena Eimi Sano Alan Kardec Barreira Roberto Murad Vessani Remo Jr. Susanna 《Journal of ocular biology, diseases, and informatics》2009,2(1):29-32
The aim of this study was to compare the intraocular pressure (IOP) profile during the modified diurnal tension curve (mDTC) using Goldman applanation tonometry (GAT) and dynamic contour tonometry (DCT) in treated glaucomatous eyes. Eligible subjects were submitted to the mDTC using GAT and DCT in this sequence. IOP measurements were performed at 8 a.m., 10 a.m., 2 p.m., and 4 p.m.. Central corneal thickness was measured using ultrasound pachymetry in the morning. Statistical analysis was performed using paired Student’s t test and Bland–Altman plot. The mean difference between DCT and GAT measurements was 0.9 mmHg. The mean ± SD IOP measurements during the mDTC were 19.68 ± 4.68, 17.63 ± 4.44, 17.25 ± 5.41, and 17.32 ± 4.25 mmHg using GAT and 19.97 ± 4.75, 18.79 ± 4.61, 19.53 ± 5.30, and 19.43 ± 5.45 mmHg using DCT. IOP measurements were higher in the morning (8 a.m.) and decreased throughout the day using both tonometers. The difference between IOP measurements using GAT and DCT was smaller in the morning and increased throughout the day. The IOP variability using GAT was higher than using DCT. Corneal biomechanical properties might help explain our findings. 相似文献
956.
957.
Igor Tadeu Lazzarotto Bresolin Mariana Borsoi-Ribeiro Juliana Rodrigues Caro Francine Petit dos Santos Marina Polesi de Castro Sonia Maria Alves Bueno 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2009,877(1-2):17-23
Tris(2-aminoethyl)amine (TREN) – a chelating agent used in IMAC – immobilized onto agarose gel was evaluated for the purification of IgG from human serum by negative chromatography. A one-step purification process allowed the recovery of 73.3% of the loaded IgG in the nonretained fractions with purity of 90–95% (based on total protein concentration and nephelometric analysis of albumin, transferrin, and immunoglobulins A, G, and M). The binding capacity was relatively high (66.63 mg of human serum protein/mL). These results suggest that this negative chromatography is a potential technique for purification of IgG from human serum. 相似文献
958.
Gul W Hammond NL Yousaf M Bowling JJ Schinazi RF Wirtz SS de Castro Andrews G Cuevas C Hamann MT 《Bioorganic & medicinal chemistry》2006,14(24):8495-8505
As part of an investigation to generate optimized drug leads from marine natural pharmacophores for the treatment of neoplastic and infectious diseases, a series of novel isoaaptamine analogs were prepared by coupling acyl halides to the C9 position of isoaaptamine (2) isolated from the Aaptos sponge. This library of new semisynthetic products was evaluated for biological activity against HIV-1, Mtb, AIDS-OI, tropical parasitic diseases, and cancer. Compound 4 showed potent activity against HIV-1 (EC50 0.47 μg/mL), compound 19 proved to possess remarkable activity against Mycobacterium intracellulare with an IC50 and MIC value of 0.15 and 0.31 μg/mL, while compounds 4 and 17 possessed anti-leishmanial activity with IC50 values of 0.1 and 0.4 μg/mL, respectively. Compounds 16 and 17 showed antimalarial activity with EC50 values of 230 and 240 ng/mL, respectively, and compound 14 exhibited an EC50 of 0.05 μM against the Leukemia cell line K-562. 相似文献
959.
960.
Costa MS Boechat N Rangel EA da Silva Fde C de Souza AM Rodrigues CR Castro HC Junior IN Lourenço MC Wardell SM Ferreira VF 《Bioorganic & medicinal chemistry》2006,14(24):8644-8653
The aim of this work was to describe the synthesis, the in vitro anti-Mycobacterium tuberculosis profile, and the structure–activity relationship (SAR) study of new N-substituted-phenyl-1,2,3-triazole-4-carbaldehydes (3a–l). The reactions of aromatic amine hydrochlorides with diazomalonaldehyde (1) produced several N-substituted-phenyl-1,2,3-triazole-4-carbaldehydes (3a–l) in moderate-to-good yields. In order to investigate the influence of the difluoromethylene group on the anti-Mycobacterium activity of these compounds, fluorination of triazoles with DAST converted the corresponding carbaldehyde compounds into new difluoromethyl derivatives (4a–l) in excellent yield. Characterization of all compounds was achieved by spectroscopic means and additional for 1-(4-methylphenyl)-1,2,3-triazole-4-carbaldehyde, 3k by X-ray crystallography. Compounds (3a–l) and (4a–l) have been screened for the inhibitory activity against Mycobacterium tuberculosis H37Rv strain (ATCC 27294) and all of them were able to inhibit the growth of the bacterium. Interestingly, 3a and 3k exhibited the best inhibition with MIC values of 2.5 μg/mL, similar to pharmaceuticals currently used in the treatment of tuberculosis. Our SAR study indicated the importance of the hydrogen bond acceptor subunit (3a–l), the position in the aromatic ring, the planarity of triazole and phenyl rings in these compounds, and a correlation between the uniform HOMO coefficient distribution and the anti-tubercular activity. The significant activity of 3a and 3k pointed them as promising lead molecules for further synthetic and biological exploration. 相似文献