全文获取类型
收费全文 | 3229篇 |
免费 | 104篇 |
国内免费 | 76篇 |
出版年
2023年 | 13篇 |
2022年 | 24篇 |
2021年 | 31篇 |
2020年 | 44篇 |
2019年 | 45篇 |
2018年 | 50篇 |
2017年 | 49篇 |
2016年 | 53篇 |
2015年 | 77篇 |
2014年 | 146篇 |
2013年 | 306篇 |
2012年 | 123篇 |
2011年 | 195篇 |
2010年 | 114篇 |
2009年 | 222篇 |
2008年 | 187篇 |
2007年 | 208篇 |
2006年 | 184篇 |
2005年 | 156篇 |
2004年 | 157篇 |
2003年 | 112篇 |
2002年 | 92篇 |
2001年 | 70篇 |
2000年 | 42篇 |
1999年 | 66篇 |
1998年 | 58篇 |
1997年 | 57篇 |
1996年 | 39篇 |
1995年 | 42篇 |
1994年 | 52篇 |
1993年 | 37篇 |
1992年 | 33篇 |
1991年 | 32篇 |
1990年 | 22篇 |
1989年 | 19篇 |
1988年 | 20篇 |
1987年 | 21篇 |
1986年 | 14篇 |
1985年 | 28篇 |
1984年 | 30篇 |
1983年 | 26篇 |
1982年 | 24篇 |
1981年 | 20篇 |
1980年 | 11篇 |
1979年 | 21篇 |
1978年 | 13篇 |
1977年 | 12篇 |
1976年 | 5篇 |
1974年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有3409条查询结果,搜索用时 15 毫秒
1.
《Bioorganic & medicinal chemistry》2020,28(21):115720
An organic small-molecular drug, 4-(1H-indol-3-yl)-2-(p-tolyl)quinazoline-3-oxide 1a was synthesized. It was employed to investigate the binding interaction and mechanism with human serum albumin (HSA). The experimental results indicated that the fluorescence quenching of HSA by 1a is a static quenching process and formation 1a-HSA complex. The site competition experiments revealed that the combination of 1a on HSA are hydrophobic interactions in the IIA domain and hydrogen bonds in IIIA domain of HSA, and the hydrophobic interactions of 1a on HSA are stronger than that of hydrogen bonds. These results were also confirmed by molecular docking theoretic analysis and ANS-hydrophobic fluorescent probe experiment. Synchronous fluorescence experiments showed that the polarity of HSA microenvironment was increase in the interaction process of 1a with HSA. The results of binding distance explored indicated that the combination distance between 1a and HSA is 3.63 nm, which is between 0.5R0 and 1.5R0, revealing the energy transfer between HSA and 1a is non-radiative. These results are very helpful for people to screen out high efficient indoloquinazoline drugs. 相似文献
2.
Synchronously growing cells of nitrogen-fixing Synechococcus sp. Miami BG 043511 were harvested periodically and the capability for hydrogen photoproduction in closed vessels was measured under hydrogen production conditions. The capability for hydrogen photoproduction in cells was correlated with that of cellular carbohydrate content. Cells with a high carbohydrate content exhibited a high capacity for hydrogen production and those with low carbohydrate content exhibited low capacity for hydrogen production. Nitrogenase activity at the onset of incubation did not coincide with a capability for the cells to produce hydrogen during the subsequent incubation period. Interestingly, when cells with a high capacity for hydrogen photoaccumulation were incubated, alternate periods of hydrogen and oxygen accumulation were observed at 12 hour intervals. About 0.5 ml of hydrogen per ml of cell suspension was accumulated in flasks during the initial 12-h incubation period. These observations indicate that the use of synchronous culture can be one of the ways of provide materials suitable not only for basic studies but also for applied aspects of hydrogen photoproduction. 相似文献
3.
《Saudi Journal of Biological Sciences》2020,27(9):2251-2260
Doxorubicin (DOX) is an anthracycline drug used for cancer treatment. However, its treatment is contiguous with toxic effects. We examined the nephroprotective potential of A. hydaspica polyphenol-rich ethyl acetate extract (AHE) against DOX persuaded nephrotoxicity. 36 male Sprague Dawley rats were randomly assorted into 6 groups. Control group received saline; DOX group: 3 mg/kg b.w. dosage of DOX intraperitoneally for 6 weeks (single dose/week). In co-treatment groups, 200 and 400 mg/kg b.w AHE was given orally for 6 weeks in concomitant with DOX (3 mg/kg b.w, i.p. injection per week) respectively. Standard group received silymarin 400 mg/kg b.w daily + DOX (single dose/week). Biochemical kidney function tests, oxidative stress markers, genotoxicity, antioxidant enzyme status, and histopathological changes were examined. DOX caused significant body weight loss and decrease kidney weight. DOX-induced marked deterioration in renal function indicators in both urine and serum, i.e., PH, specific gravity, total protein, albumin, urea, creatinine, uric acid, globulin, blood urea nitrogen, etc. Also, DOX treatment increases renal tissue oxidative stress markers, while lower antioxidant enzymes in tissue along with degenerative alterations in the renal tissue compared to control rats. AHE co-treatment ameliorates DOX-prompted changes in serum and urine chemistry. Likewise, AHE treatment decreases sensitive markers of oxidative stress and prevented DNA damages by enhancing antioxidant enzyme levels. DOX induction in rats also caused DNA fragmentation which was restored by AHE co-treatment. Moreover, the histological observations evidenced that AHE effectively rescued the kidney tissue from DOX interceded oxidative damage. Our results suggest that co-treatment of AHE markedly improve DOX-induced deleterious effects in a dose-dependent manner. The potency of AHE co-treatment at 400 mg/kg dose is similar to silymarin. These outcomes revealed that A. hydaspica AHE extract might serve as a potential adjuvant that avoids DOX-induced nephrotoxicity. 相似文献
4.
Visualization of the microbody division inCyanidioschyzon merolae with the fluorochrome brilliant sulfoflavin 总被引:1,自引:0,他引:1
M. Miyagishima R. Itoh K. Toda H. Takahashi H. Kuroiwa T. Kuroiwa 《Protoplasma》1998,201(1-2):115-119
Summary A novel procedure is described for fluorescence staining of microbodies, which can be applied quickly and easily. We developed this technique of microbody staining with the unicellular red algaCyanidioschyzon merolae. Cyanidioschyzon merolae only contains a single chloroplast, mitochondrion, and microbody per cell, and the mitotic cycle and the organelle division cycle are easily synchronized. Knowing that the concentration of H2O2 in the microbody is higher than it is in the cytosol and other cell components, we attempted to visualize the microbody by using fluorescence microscopy to detect H2O2. Brilliant sulfoflavin (BSF), used for detecting Fe2+ in analytical chemistry, fluoresces when it reacts with Fe2+ and H2C2. We were able to specifically stain microbodies with BSF, under acidic conditions (pH 3.0 or pH 2.5) with blue-light excitation. Using this procedure, we observed division of the microbody and the effect of aphidicolin on the microbody. We also discovered that microbody division is regulated by the cell nucleus and follows division of the cell nucleus. 相似文献
5.
Ranganathan Santhanam 《Inorganica chimica acta》2008,361(2):473-478
A novel method of preparation of hexahydroaluminate complexes M3AlH6 (M = Li, Na or K) from the corresponding alkali metal hydride and tetrahydroaluminate has been explored, using dimethyl ether (Me2O) as a solvent at near-ambient temperatures. The results are compared with those obtained using a recently established mechanochemical approach. Characterization of the products by powder X-ray diffraction revealed M3AlH6 to be formed in high yield for M = Li and Na, but not for M = K. The attempted preparation of Li2NaAlH6 and Li2KAlH6 was unsuccessful. 相似文献
6.
An oxidative and salinity stress induced peroxisomal ascorbate peroxidase from Avicennia marina: Molecular and functional characterization 总被引:1,自引:0,他引:1
Kumaresan Kavitha Gayatri Venkataraman Ajay Parida 《Plant Physiology and Biochemistry》2008,46(8-9):794-804
APX (EC, 1.11.1.11) has a key role in scavenging ROS and in protecting cells against their toxic effects in algae and higher plants. A cDNA encoding a peroxisomal ascorbate peroxidase, Am-pAPX1, was isolated from salt stressed leaves of Avicennia marina (Forsk.) Vierh. by EST library screening and its expression in the context of various environmental stresses was investigated. Am-pAPX1 contains an ORF of 286 amino acids coding for a 31.4kDa protein. The C-terminal region of the Am-pAPX1 ORF has a putative transmembrane domain and a peroxisomal targeting signal (RKKMK), suggesting peroxisomal localization. The peroxisomal localization of Am-pAPX1 was confirmed by stable transformation of the GFP-(Ala)(10)-Am-pAPX1 fusion in tobacco. RNA blot analysis revealed that Am-pAPX1 is expressed in response to salinity (NaCl) and oxidative stress (high intensity light, hydrogen peroxide application and excess iron). The isolated genomic clone of Am-pAPX1 was found to contain nine exons. A fragment of 1616bp corresponding to the 5' upstream region of Am-pAPX1 was isolated by TAIL-PCR. In silico analysis of this sequence reveals the presence of putative light and abiotic stress regulatory elements. 相似文献
7.
Zac Yates Kannan Gunasekaran Hongxing Zhou Zhonghua Hu Zhi Liu Randal R. Ketchem Boxu Yan 《The Journal of biological chemistry》2010,285(24):18662-18671
Hydroxyl radicals induce hinge cleavage in a human IgG1 molecule via initial radical formation at the first hinge Cys231 followed by electron transfer to the upper hinge residues. To enable engineering of a stable monoclonal antibody hinge, we investigated the role of the hinge His229 residue using structure modeling and site-directed mutagenesis. Direct involvement of His229 in the reaction mechanism is suggested by a 75–85% reduction of the hinge cleavage for variants in which His229 was substituted with either Gln, Ser, or Ala. In contrast, mutation of Lys227 to Gln, Ser, or Ala increased hinge cleavage. However, the H229S/K227S double mutant shows hinge cleavage levels similar to that of the single H229S variant, further revealing the importance of His229. Examination of the hinge structure shows that His229 is capable of forming hydrogen bonds with surrounding residues. These observations led us to hypothesize that the imidazole ring of His229 may function to facilitate the cleavage by forming a transient radical center that is capable of extracting a proton from neighboring residues. The work presented here suggests the feasibility of engineering a new generation of monoclonal antibodies capable of resisting hinge cleavage to improve product stability and efficacy. 相似文献
8.
The interactions of the cellulose molecule with several anions, including acetate , alkyl phosphate, tetrafluoroborate and hexafluorophosphate anions which are most commonly involved in the imidazolium ionic liquids (ILs), have been studied by performing density functional theory calculations. Based on calculated geometries, energies, IR characteristics, and electronic properties of the cellulose-anion complexes, it is found that the strength of interactions of anions with cellulose follows the order: acetate anion > alkyl phosphate anion > tetrafluoroborate anion > hexafluorophosphate anion, which is consistent with the experimentally observed solubility trend of cellulose in the corresponding imidazolium-based ILs. The present study may provide basic aids to some extent for understanding the dissolution behavior of cellulose in the imidazolium-based ILs. 相似文献
9.
Methanol production resulting from the demethoxylation of lignin-related substances by Phanerochaete chrysosporium K-3 was studied in the presence or absence of glutamic acid in order to determine if methanol formation involved the ligninolytic system of the fungus. The general pattern was that methanol formation, calculated as percentage of theoretical yield, decreased in the order guaiacyl > syringyl > veratryl (3,4-dimethoxy) compounds. Methoxyhydroquinone and vanillic acid were most easily demethoxylated, while methanol production decreased with increasing molecular weight for the same type of structure (i.e. guaiacyl). Glutamic acid inhibited the demethoxylation of many of the compounds tested. The demethoxylation of the 4-methoxy group of veratric acid was particularly inhibited by glutamic acid suggesting a participation of the ligninolytic system, while the 3-methoxy group was influenced to a lesser extent.
The demethoxylating enzyme acting on lignin-related phenols is probably a peroxidase, while the identity of the enzyme demethoxylating dimethoxy compounds is not known with certainty, although a peroxidase type of enzyme reaction is anticipated also here. 相似文献
The demethoxylating enzyme acting on lignin-related phenols is probably a peroxidase, while the identity of the enzyme demethoxylating dimethoxy compounds is not known with certainty, although a peroxidase type of enzyme reaction is anticipated also here. 相似文献
10.
H2S, the most recently discovered gasotransmitter, might in fact be the evolutionary matriarch of this family, being both ancient and highly reduced. Disruption of γ-cystathionase in mice leads to cardiovascular dysfunction and marked hypertension, suggesting a key role for this enzyme in H2S production in the vasculature. However, patients with inherited deficiency in γ-cystathionase apparently do not present vascular pathology. A mitochondrial pathway disposes sulfide and couples it to oxidative phosphorylation while also exposing cytochrome c oxidase to this metabolic poison. This report focuses on the biochemistry of H2S biogenesis and clearance, on the molecular mechanisms of its action, and on its varied biological effects. 相似文献