全文获取类型
收费全文 | 1943篇 |
免费 | 130篇 |
国内免费 | 54篇 |
出版年
2024年 | 7篇 |
2023年 | 9篇 |
2022年 | 43篇 |
2021年 | 76篇 |
2020年 | 40篇 |
2019年 | 34篇 |
2018年 | 67篇 |
2017年 | 64篇 |
2016年 | 95篇 |
2015年 | 102篇 |
2014年 | 109篇 |
2013年 | 152篇 |
2012年 | 117篇 |
2011年 | 165篇 |
2010年 | 102篇 |
2009年 | 77篇 |
2008年 | 83篇 |
2007年 | 84篇 |
2006年 | 66篇 |
2005年 | 77篇 |
2004年 | 58篇 |
2003年 | 53篇 |
2002年 | 46篇 |
2001年 | 20篇 |
2000年 | 22篇 |
1999年 | 27篇 |
1998年 | 20篇 |
1997年 | 12篇 |
1996年 | 18篇 |
1995年 | 12篇 |
1994年 | 11篇 |
1993年 | 8篇 |
1992年 | 13篇 |
1991年 | 13篇 |
1990年 | 12篇 |
1989年 | 14篇 |
1987年 | 12篇 |
1986年 | 9篇 |
1985年 | 16篇 |
1984年 | 10篇 |
1983年 | 15篇 |
1982年 | 11篇 |
1981年 | 7篇 |
1979年 | 8篇 |
1977年 | 7篇 |
1976年 | 11篇 |
1972年 | 6篇 |
1971年 | 7篇 |
1969年 | 10篇 |
1968年 | 6篇 |
排序方式: 共有2127条查询结果,搜索用时 406 毫秒
81.
82.
Amena Ali Abuzer Ali Abu Tahir Mohammed Afroz Bakht Mohamed Jawed Ahsan 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):135
We reported herein an efficient, environmentally friendly synthesis of hydrazine carboxamides (6a–l) in a water-glycerol (6:4) solvent system using ultrasonic irradiation. Ultrasonicated reactions were found to be much faster and more productive than conventional synthesis. The prepared compounds (6a–l) were tested against nine panels of 60 cancer cell lines according to the National Cancer Institute (NCI US) protocol. N-(4-Chlorophenyl)-2-(2-oxoindolin-3-ylidene)hydrazine-1-carboxamide (6b) was discovered to be promising anticancer agents with higher sensitivity against CCRF-CEM, HOP-92, UO-31, RMPI-8226, HL-60(TB), and MDA-MB-468 with percent growth inhibitions (%GIs) of 143.44, 33.46, 33.21, 33.09, 29.81, and 29.55 respectively. Compounds (6a–l) tested showed greater anticancer activity than Imatinib, except for compound 6k. Compounds 6b and 6c were found to be lethal on the CCRF-CEM leukaemia cell line, with %GIs of 143.44 and 108.91, respectively. Furthermore, molecular docking analysis was performed to investigate ligand binding affinity at the active site of epidermal growth factor (EGFR). 相似文献
83.
Abasic sites are highly mutagenic lesions in DNA that arise as intermediates in the excision repair of modified bases. These sites are generated by the action of damage-specific DNA glycosylases and are converted into downstream intermediates by the specific activity of apurinic/apyrimidinic endonucleases. Enzymes in both families have been observed in crystal structures to impose deformations on the abasic-site DNA, including DNA kinking and base flipping. On the basis of these apparent protein-induced deformations, we propose that altered conformation and dynamics of abasic sites may contribute to the specificity of these repair enzymes. Previously, measurements of the steady-state fluorescence of the adenine analogue 2-aminopurine (2AP) opposite an abasic site demonstrated that binding of divalent cations could induce a conformational change that increased the accessibility of 2AP to solute quenching [Stivers, J. T. (1998) Nucleic Acids Res. 26, 3837-44]. We have performed time-resolved fluorescence experiments to characterize the states involved in this conformational change. Interpretation of these studies is based on a recently developed model attributing the static and dynamic fluorescence quenching of 2AP in DNA to aromatic stacking and collisional interactions with neighboring bases, respectively (see the preceding paper in this issue). The time-resolved fluorescence results indicate that divalent cation binding shifts the equilibrium of the abasic site between two conformations: a "closed" state, characterized by short average fluorescence lifetime and complex decay kinetics, and an "open" state, characterized by monoexponential decay with lifetime approximately that of the free nucleoside. Because the lifetime and intensity decay kinetics of 2AP incorporated into DNA are sensitive primarily to collisional interactions with the neighboring bases, the absence of dynamic quenching in the open state strongly suggests that the fluorescent base is extrahelical in this conformation. Consistent with this interpretation, time-resolved quenching studies reveal that the open state is accessible to solute quenching by potassium iodide, but the closed state is not. Greater static quenching is observed in the abasic site when the fluorescent base is flanked by 5'- and 3'-thymines than in the context of 5'- and 3'-adenines, indicating that 2AP is more stacked with the neighboring bases in the former sequence. These results imply that the conformation of the abasic site varies in a sequence-dependent manner. Undamaged sequences in which the abasic site is replaced by thymine do not exhibit an open state and have different levels of both static and dynamic quenching than their damaged homologues. These differences in structure and dynamics may be significant determinants of the high specific affinity of repair enzymes for the abasic site. 相似文献
84.
85.
Yavuzer R Tuncer S Başterzi Y Işik I Sari A Latifoğlu O 《Plastic and reconstructive surgery》2004,113(1):34-44
The orbital floor is one of the most frequently damaged parts of the maxillofacial skeleton during facial trauma. Unfavorable aesthetic and functional outcomes are frequent when it is treated inadequately. The treatment consists of spanning the floor defect with a material that can provide structural support and restore the orbital volume. This material should also be biocompatible with the surrounding tissues and easily reshaped to fit the orbital floor. Although various autografts or synthetic materials have been used, there is still no consensus on the ideal reconstruction method of orbital floor defects. This study evaluated the applicability of solvent-preserved cadaveric cranial bone graft and its preliminary results in the reconstruction of the orbital floor fractures. Twenty-five orbital floor fractures of 21 patients who underwent surgical repair with cadaveric bone graft during a 2-year period were included in this study. Pure blowout fractures were determined in nine patients, whereas 12 patients had other accompanying maxillofacial fractures. Of the 21 patients, 14 had clinically evident diplopia (66.7 percent), 12 of them had enophthalmos (57.1 percent), and two of them had gaze restriction preoperatively. Reconstruction of the floor of the orbit was performed following either the subciliary or the transconjunctival approach. A cranial allograft was placed over the defect after sufficient exposure. The mean follow-up period was 9 months. Postoperative diplopia, enophthalmos, eye motility, cosmetic appearance, and complications were documented. None of the patients had any evidence of diplopia, limited eye movement, inflammatory reactions in soft tissues, infection, or graft extrusion in the postoperative period. Providing sufficient orbital volume, no graft resorption was detected in computed tomography scan controls. None of the implants required removal for any reason. Enophthalmos was seen in one patient, and temporary scleral show lasting up to 3 to 6 weeks was detected in another three patients. Satisfactory cosmetic results were obtained in all patients. This study showed that solvent-preserved bone, which is a nonsynthetic, human-originated, processed bioimplant, can be safely used in orbital floor repair and can be considered as another reliable treatment alternative. 相似文献
86.
87.
The aim of the present study is to determine whether patients with primary spontaneous pneumothorax (PSP) are subject to oxidative stress. For this purpose, we measured the activities of red blood cell superoxide dismutase, which is an antioxidant enzyme, and the level of plasma malondialdehyde, which is one of the lipid peroxidation markers, in a group of patients with PSP. The study was carried out with 16 patients with PSP and 24 healthy individuals. The two groups were similar to each other in terms of sex, age and smoking attitudes. Erythrocyte superoxide dismutase activity was found to be significantly lower in patients with PSP than in the control group (p < 0.01). The plasma malondialdehyde levels were significantly high in patients with PSP (p < 0.01). Our results suggest that oxidative stress may contribute to the pathogenesis of PSP. 相似文献
88.
BACKGROUND: To determine the presence of Helicobacter species in the liver biopsy specimens from children with various chronic liver diseases as data in adult literature suggests a possible role of these bacteria in their pathogenesis. MATERIALS AND METHODS: Paraffin sections of 61 liver biopsies of pediatric patients with miscellaneous diseases and autopsy liver tissue from 10 control subjects with no evidence of preexisting liver disease were examined for the presence of Helicobacter species by a genus-specific seminested polymerase chain reaction (PCR) assay. PCR-products of positive samples were further characterized by denaturing gradient gel electrophoresis (DGGE) and DNA-sequence analysis. Based on those results, a seminested PCR assay for H. ganmani was developed and applied to the samples. RESULTS: On analysis, 40/61 patient samples were positive in the genus-specific Helicobacter PCR and 4/10 from the control group. The nucleotide sequences of 16S rDNA fragments were 99-100% similar to mainly Helicobacter sp. 'liver' and H. ganmani. PCR-products similar to H. canis and H. bilis were also found. The 16S rDNAs of control specimens showed similarity to Helicobacter sp. 'liver'. In the H. ganmani-specific PCR analysis 19 patients, but none of the controls, were positive. CONCLUSIONS: Amplified Helicobacter 16S rDNAs were related to Helicobacter sp. 'liver' or H. ganmani in liver biopsy specimens of pediatric patients. The possible significance of Helicobacter species in pediatric liver diseases needs to be evaluated further in prospective studies. 相似文献
89.
In this work it is shown how anthropological data are among the most needed factors in ergonomical valorization of crew working spaces. Ship's working or living environment involves many unique human factors, which should be specially considered in our case as limitation of crew space. In this work we have chosen ships of different years of construction to prove this tendency. As a micro study, the work posture analysis using the pulling force experiment is performed in order to determine lumbar moment, intra-abdominal pressure as a measure of evaluating and comparing different crew work positions. As a macro-study, the "crew work posture analysis" was carried out by the use of the data collected from real cases. The most probable work postures in different spaces of a ship are classified and after some corrections of the work place the profile and its grade were determined. The "statistical analysis for real ship's spaces" is also performed, as well as another macro study, in order to show some real designed ship spaces from the point of view of the allocated volume. 相似文献
90.
Spangfort MD Mirza O Ipsen H Van Neerven RJ Gajhede M Larsen JN 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(6):3084-3090
Specific allergy vaccination is an efficient treatment for allergic disease; however, the development of safer vaccines would enable a more general use of the treatment. Determination of molecular structures of allergens and allergen-Ab complexes facilitates epitope mapping and enables a rational approach to the engineering of allergen molecules with reduced IgE binding. In this study, we describe the identification and modification of a human IgE-binding epitope based on the crystal structure of Bet v 1 in complex with the BV16 Fab' fragment. The epitope occupies approximately 10% of the molecular surface area of Bet v 1 and is clearly conformational. A synthetic peptide representing a sequential motif in the epitope (11 of 16 residues) did not inhibit the binding of mAb BV16 to Bet v 1, illustrating limitations in the use of peptides for B cell epitope characterization. The single amino acid substitution, Glu(45)-Ser, was introduced in the epitope and completely abolished the binding of mAb BV16 to the Bet v 1 mutant within a concentration range 1000-fold higher than wild type. The mutant also showed up to 50% reduction in the binding of human polyclonal IgE, demonstrating that glutamic acid 45 is a critical amino acid also in a major human IgE-binding epitope. By solving the three-dimensional crystal structure of the Bet v 1 Glu(45)-Ser mutant, it was shown that the change in immunochemical activity is directly related to the Glu(45)-Ser substitution and not to long-range structural alterations or collapse of the Bet v 1 mutant tertiary structure. 相似文献