首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   2477篇
  免费   140篇
  国内免费   2篇
  2024年   7篇
  2023年   36篇
  2022年   76篇
  2021年   128篇
  2020年   55篇
  2019年   63篇
  2018年   94篇
  2017年   69篇
  2016年   114篇
  2015年   116篇
  2014年   126篇
  2013年   174篇
  2012年   171篇
  2011年   174篇
  2010年   102篇
  2009年   85篇
  2008年   108篇
  2007年   103篇
  2006年   99篇
  2005年   82篇
  2004年   93篇
  2003年   68篇
  2002年   60篇
  2001年   46篇
  2000年   32篇
  1999年   19篇
  1998年   21篇
  1997年   17篇
  1996年   9篇
  1995年   15篇
  1994年   8篇
  1993年   12篇
  1992年   15篇
  1991年   16篇
  1990年   8篇
  1989年   7篇
  1988年   13篇
  1986年   11篇
  1985年   14篇
  1984年   9篇
  1982年   7篇
  1981年   9篇
  1980年   9篇
  1979年   9篇
  1978年   12篇
  1977年   9篇
  1976年   9篇
  1974年   9篇
  1973年   10篇
  1969年   9篇
排序方式: 共有2619条查询结果,搜索用时 593 毫秒
991.
DMBA (7,12-dimethylbenz[a]anthracene) is a polycyclic aromatic hydrocarbon (PAH) known to cause tumors in rats. Selenium is an essential element with physiological non-enzymatic antioxidant properties. Because of the health problems induced by many environmental pollutants, many efforts have been undertaken in evaluating the relative antioxidant potential of selenium and synthetic organoselenium compounds. In this study, adult female Wistar rats were treated with DMBA and the novel organoselenium compounds (1-isopropyl-3-methylbenzimidazole-2-selenone [SeI] and 1,3-di-p-methoxybenzylpyrimidine-2-selenone [SeII]) in the determined doses. The protective effects of novel synthetic organoselenium compounds (SeI and SeII) against DMBA-induced changes in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and total glutathione (GSH) and malone-dialdehyde (MDA) levels of rat heart and brain were investigated. It was determined that SeI and SeII fully or partially restored enzyme activity. It was also found that lipid peroxidation was also decreased in SeI and SeII treated groups. Consequently, it was determined that novel synthetic organoselenium compounds (SeI and SeII) provided protection of antioxidant activity, and protection against lipid peroxidation measured as MDA in SeI and SeII treated groups was provided by novel synthesized organoselenium compounds. The ability of the organoselenium compounds to prevent oxidative damage induced by DMBA in rats was rationalized.  相似文献   
992.
Gaucher disease (GD) is an autosomal recessive inborn error of metabolism, resulting from a deficiency of the enzyme glucocerebrosidase, causing an accumulation of the glycolipid glucocerebroside within lysosomes of macrophages in the reticuloendothelial system. Three major clinical forms have been assigned and more than 200 gene mutations have been identified. We herein report a Lebanese boy born with a novel combined mutation L371V/Rec-NciI, who presented with moderate-severe type 1 GD. An overview of the clinical and biomarker improvement following enzyme replacement therapy with imiglucerase is described in a follow-up of 30 months. Imiglucerase seems to be efficacious in decreasing the severity of the disease associated with this mutation. However, a high dose may be required to achieve optimal growth, platelet count, and hemoglobin level.  相似文献   
993.
The main objective of the present study was to improve the quality of pulp and paper industrial wastewater of two local mills RAKTA and El-Ahlia, Alexandria, Egypt, and to bring their pollutant contents to safe discharge levels. Quality improvement was carried out using integrated chemical and biological treatment approaches after their optimization. Chemical treatment (alum, lime, and ferric chloride) was followed by oxidation using hydrogen peroxide and finally biological treatment using activated sludge (90 min for RAKTA and 60 min for El-Ahlia effluents). Chemical coagulation produced low-quality effluents, while pH adjustment during coagulation treatment did not enhance the quality of the effluents. Maximum removal of the tested pollutants was achieved using the integrated treatment and the pollutants recorded residual concentrations (RCs) of 34.67, 17.33, 0.13, and 0.43 mg/l and 15.0, 11.0, 0.0, and 0.13 mg/l for chemical oxygen demand (COD), biochemical oxygen demand (BOD5), tannin and lignin, and silica in RAKTA and El-Ahlia effluents, respectively, all of which were below their maximum permissible limits (MPLs) for the safe discharge into water courses. Specific oxygen uptake rate (SOUR) and sludge volume index (SVI) values reflect good conditions and healthy activated sludge. Based on the previous results, optimized conditions were applied as bench scale on the raw effluents of RAKTA and El-Ahlia via the batch chemical and the biological treatment sequences proposed. For RAKTA effluents, the sequence was as follows: (1) coagulation with 375 mg/l FeCl3, (2) oxidation with 50 mg/l hydrogen peroxide, and (3) biological treatment using activated sludge with 2,000 mg/l initial concentration and 90 min hydraulic retention time (HRT), while for El-Ahlia raw effluents, the sequence was (1) coagulation with 250 mg/l FeCl3, (2) oxidation with 45 mg/l hydrogen peroxide, and (3) biological treatment using activated sludge with 2,000 mg/l initial concentration and 60 min HRT. In conclusion, results confirmed that the application of the proposed sequential treatments removed almost all COD, BOD5, high molecular weight compounds, and silica from RAKTA and El-Ahlia influents and produced high-quality effluents, thus achieving the main objective of this study.  相似文献   
994.
The public markets aren't what they used to be and venture capitalists are seeking investments with shorter timelines. But the good news is several new sources of financing are becoming available.  相似文献   
995.
Motile Sperm Organelle Morphology Examination (MSOME) constitutes a real improvement in ART management and outcome, as it allows detection of specific sperm anomalies on living cells, which cannot be detected by routine analysis. MSOME applied to the selection of sperm injected into the oocyte is called IMSI (Intracytoplasmic Morphologically Selected sperm Injection) and is associated with a considerable improvement of implantation, clinical pregnancy and delivery rates. A high-power microscope (X 2,000 to X 10,000) and video enhancement system are necessary and technical limitations are related to cryptozoospermia and/or severe teratozoospermia. Compared to routine sperm morphology assessment, MSOME allows the detection of subtle cephalic anomalies, such as vacuoles. These vacuoles seem to have a deleterious effect on fertilization and embryo developmentin vitro. These observations have led to a detailed classification of anomalies and this morphological diagnosis on living sperm demonstrates that most sperm selected for conventional ICSI at X 400 are actually abnormal on MSOME at X 6,000 or more. In addition to the very good results obtained in IMSI, this new approach opens up interesting prospects concerning the relationship between the phenotype of the injected sperm and its fertilization capacity and embryo development. In terms of diagnosis, MSOME could be used to select and study homogeneous groups of normal sperm or homogeneous groups of sperm exhibiting the same well defined anomaly. Such studies, associated with fine analysis of injected sperm and follow-up of each oocyte and each embryo, should provide more information about the relationship between sperm structure and function and should help to define the relevant indications for IMSI and the choice of spermatozoa to be injected.  相似文献   
996.
Polymerization of 20% neutralized acrylic acid (Na form), AA, in presence of Karaya gum, KG, or tamarind seed gum, TG, at AA/gum weight ratio of 1/1 and 2/1 results in PAA/KG1, PAA/KG2, PAA/TG1 and PAA/TG2 adducts, respectively (where the suffix 1 or 2 stands for AA/gum ratios of 1/1 or 2/1). Infra red spectra of adducts are examined. Aqueous pastes of adducts, native gums and GG are of non-Newtonian thixotropic flow within a shear rate range of 4–40 s−1. Adduct pastes (7.5% w/v) are of higher apparent viscosities (η) than their native gums or GG, and pastes of TG adducts are of higher η than KG adducts. Except for PAA/TG2 adduct, the power law does not correlate well to the other pastes. Preliminary trials showed that adducts are excellent thickeners for reactive and acid printing on wool, silk and nylon 6. Prints by adducts are of higher color strength than those by native gums or GG. GG paste was completely destroyed after storing for 7 days, whereas η of pastes of adducts and native gums were noticeably decreased upon storing.  相似文献   
997.
A comparative evaluation of three washing methods for removing exogenous elemental contamination from fetal scalp hair is described. A total of 12 samples, including 6 from normal pregnancies and 6 from abruptio placentae (AP) cases, were used. Each was divided into four subsamples, with one left unwashed for comparison, while three were subjected to one of the three washing methods. The first consisted of agitating hair for 5 min in sequential and equal measures (30 ml) of acetone and water, followed by rinsing with acetone, and the process repeated twice. In the second and third, hair was agitated for 30 min in aqueous solutions of sodium lauryl sulfate (0.5%, w/v), and Triton X-100 (0.5%, v/v), respectively, followed by sequential rinsing with deionized water and acetone. After drying and microwave-assisted digestion in concentrated nitric acid, the subsamples' concentrations of zinc, copper, cadmium, lead, mercury and selenium were determined using inductively coupled mass spectrometry. All washed subsamples, irrespective of washing method used, had lower elemental concentrations than the corresponding, unwashed subsamples. These differences, taken as presumptive indicators of exogenous contamination, showed only small variations (<5%) between the three washing methods, irrespective of element, mode of delivery, and obstetric outcome. However, the contamination levels elicited by each of the three methods varied in magnitude according to individual elements, with those of copper being highest, followed by those of zinc, cadmium, mercury, selenium, and lead. They also varied according to obstetric outcome, being highest in the AP subsamples, while in the normal pregnancy group, copper and zinc contamination levels in the subsamples from neonates delivered by elective caesarean section were higher than in those from normal-delivery neonates. The data from this study suggest that the three washing methods used have comparable efficacies in removing exogenous elemental contamination from fetal hair, further inferring that it is probably a simple biological matrix to decontaminate. Possible contributory factors are discussed and contrasted with those affecting adult hair.  相似文献   
998.
Wheat flavone O-methyltransferase catalyzes three sequential methylations of the flavone tricetin. Like other flavonoid O-methyltransferases, the protein is a homodimer. We demonstrate, using analytical ultracentrifugation, that perchlorate dissociates the dimer into monomers. The resulting monomers retain all their catalytic capacity, including the ability to catalyze the three successive methylations. We show, using isothermal titration calorimetry, that the binding constant for S-adenosyl-L-methionine does not change significantly as the protein dissociates. The second substrate, tricetin, binds to the dimers but could not be tested with the monomers. CD, UV and fluorescence spectroscopy show that there are substantial changes in the structure of the protein as it dissociates. The fact that there are differences between the monomers and dimers even as the monomers maintain activity may be the result of the very low catalytic capacity of this enzyme. Maximal turnover numbers for the dimers and monomers are only about 6-7 per minute. Even though the binding pockets for S-adenosyl-L-methionine, tricetin, selgin and tricin are intact, selection of a catalytically competent structure may be a very slow step during catalysis.  相似文献   
999.

Background

The Mitotic Spindle Assembly Checkpoint (MSAC) is an evolutionary conserved mechanism that ensures the correct segregation of chromosomes by restraining cell cycle progression from entering anaphase until all chromosomes have made proper bipolar attachments to the mitotic spindle. Its malfunction can lead to cancer.

Principle Findings

We have constructed and validated for the human MSAC mechanism an in silico dynamical model, integrating 11 proteins and complexes. The model incorporates the perspectives of three central control pathways, namely Mad1/Mad2 induced Cdc20 sequestering based on the Template Model, MCC formation, and APC inhibition. Originating from the biochemical reactions for the underlying molecular processes, non-linear ordinary differential equations for the concentrations of 11 proteins and complexes of the MSAC are derived. Most of the kinetic constants are taken from literature, the remaining four unknown parameters are derived by an evolutionary optimization procedure for an objective function describing the dynamics of the APC:Cdc20 complex. MCC:APC dissociation is described by two alternatives, namely the “Dissociation” and the “Convey” model variants. The attachment of the kinetochore to microtubuli is simulated by a switching parameter silencing those reactions which are stopped by the attachment. For both, the Dissociation and the Convey variants, we compare two different scenarios concerning the microtubule attachment dependent control of the dissociation reaction. Our model is validated by simulation of ten perturbation experiments.

Conclusion

Only in the controlled case, our models show MSAC behaviour at meta- to anaphase transition in agreement with experimental observations. Our simulations revealed that for MSAC activation, Cdc20 is not fully sequestered; instead APC is inhibited by MCC binding.  相似文献   
1000.

Background

Schistosoma mansoni exists in a complex environmental milieu that may select for significant evolutionary changes in this species. In Kenya, the sympatric distribution of S. mansoni with S. rodhaini potentially influences the epidemiology, ecology, and evolutionary biology of both species, because they infect the same species of snail and mammalian hosts and are capable of hybridization.

Methodology/Principal Findings

Over a 2-year period, using a molecular epidemiological approach, we examined spatial and temporal distributions, and the overlap of these schistosomes within snails, in natural settings in Kenya. Both species had spatially and temporally patchy distributions, although S. mansoni was eight times more common than S. rodhaini. Both species were overdispersed within snails, and most snails (85.2% for S. mansoni and 91.7% for S. rodhaini) only harbored one schistosome genotype. Over time, half of snails infected with multiple genotypes showed a replacement pattern in which an initially dominant genotype was less represented in later replicates. The other half showed a consistent pattern over time; however, the ratio of each genotype was skewed. Profiles of circadian emergence of cercariae revealed that S. rodhaini emerges throughout the 24-hour cycle, with peak emergence before sunrise and sometimes immediately after sunset, which differs from previous reports of a single nocturnal peak immediately after sunset. Peak emergence for S. mansoni cercariae occurred as light became most intense and overlapped temporally with S. rodhaini. Comparison of schistosome communities within snails against a null model indicated that the community was structured and that coinfections were more common than expected by chance. In mixed infections, cercarial emergence over 24 hours remained similar to single species infections, again with S. rodhaini and S. mansoni cercarial emergence profiles overlapping substantially.

Conclusions/Significance

The data from this study indicate a lack of obvious spatial or temporal isolating mechanisms to prevent hybridization, raising the intriguing question of how the two species retain their separate identities.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号