全文获取类型
收费全文 | 2370篇 |
免费 | 143篇 |
国内免费 | 94篇 |
专业分类
2607篇 |
出版年
2024年 | 16篇 |
2023年 | 28篇 |
2022年 | 34篇 |
2021年 | 33篇 |
2020年 | 68篇 |
2019年 | 59篇 |
2018年 | 73篇 |
2017年 | 45篇 |
2016年 | 48篇 |
2015年 | 65篇 |
2014年 | 74篇 |
2013年 | 172篇 |
2012年 | 82篇 |
2011年 | 65篇 |
2010年 | 66篇 |
2009年 | 96篇 |
2008年 | 86篇 |
2007年 | 97篇 |
2006年 | 120篇 |
2005年 | 127篇 |
2004年 | 108篇 |
2003年 | 104篇 |
2002年 | 102篇 |
2001年 | 99篇 |
2000年 | 67篇 |
1999年 | 64篇 |
1998年 | 59篇 |
1997年 | 55篇 |
1996年 | 57篇 |
1995年 | 46篇 |
1994年 | 58篇 |
1993年 | 47篇 |
1992年 | 39篇 |
1991年 | 33篇 |
1990年 | 33篇 |
1989年 | 27篇 |
1988年 | 28篇 |
1987年 | 28篇 |
1986年 | 13篇 |
1985年 | 12篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1982年 | 17篇 |
1981年 | 12篇 |
1980年 | 17篇 |
1979年 | 9篇 |
1978年 | 1篇 |
1977年 | 4篇 |
1975年 | 1篇 |
1973年 | 2篇 |
排序方式: 共有2607条查询结果,搜索用时 15 毫秒
121.
锌指结构:最普遍的核酸识别元件 总被引:3,自引:0,他引:3
锌指是最大的DNA结合蛋白家庭,是识别DNA最有效、最成功的一种结构元件。其模块性结构特点及与核酸作用的相对简单性,使其成为研究蛋白-核酸相互作用的理想材料,以及人为设计筛选新的核酸结合蛋白的最佳元件。 相似文献
122.
E. Carpenè O. Cattani G. P. Serrazanetti G. Fedrizzi P. Cortesi 《Journal of fish biology》1990,37(2):293-299
Zinc and copper were detected in several tissues of fresh and saltwater fish. Liver concentrations varied widely, with respect to the storage and detoxication functions of the organ. In muscular tissues the two metals are linked to aerobic metabolism being higher in the heart and lower in the white muscle. High levels of zinc were found in the female gonad, while in the brain zinc has been shown to be more constant and possibly regulated better than copper. In sea bass supplemented with artificial diets no correlation was found between the metal content in the diet and that of the tissue. In goldfish attempts using gel filtration to isolate specific metal binding proteins of low molecular weight gave negative results, the metals were mostly bound to ligands excluded from the gel. 相似文献
123.
Effects of metals on enzyme activity in plants 总被引:16,自引:0,他引:16
Abstract. Uptake of phytotoxic amounts of metal by higher plants or algae can result in inhibition of several enzymes, and in increase in activity (= induction) of others. Two mechanisms of enzyme inhibition predominate: (1) binding of the metal to sulphydryl groups, involved in the catalytic actionor structural integrity of enzymes, and (2) deficiency of an essential metal in metalloproteins or metal-protein complexes, eventually combined with substitution of the toxic metal for the deficient element. Metal accumulation in the cellular compartment of the enzyme is a prerequisite for enzyme inhibition in vivo. The induction of some enzymes is considered to play a significant role in the stress metabolism, induced by metal phytotoxicity. Peroxidase induction is likely to be related to oxidative reactions at the biomembrane; several enzymes of the intermediary metabolism might be stimulated to compensate for metal-sensitive photosynthetic reactions. The induction of enzymes and metal-specific changes in isoperoxidase pattern can be used as diagnostic criteria to evaluate the phytotoxicity of soils, contaminated by several metals. Lines for future research on metal phytotoxicity are proposed, involving the study of inhibition and induction of enzymes at the different cell membranes (especially the plasmamembrane) in vivo. 相似文献
124.
Zinc finger motif for single-stranded nucleic acids? investigations by nuclear magnetic resonance 总被引:8,自引:0,他引:8
M F Summers 《Journal of cellular biochemistry》1991,45(1):41-48
Nuclear magnetic resonance (NMR) methods have been used to address issues regarding the relevance and feasibility of zinc binding to "zinc finger-like" sequences of the type C-X2-C-X4-H-X4-C [referred to as CCHC or retroviral-type (RT) zinc finger sequences]. One-dimensional (1D) NMR experiments with an 18-residue synthetic peptide containing the amino acid sequence of an HIV-1 RT-zinc finger domain (HIV1-F1) indicate that the sequences are capable of binding zinc tightly and stoichiometrically. 1H-113Cd spin echo difference NMR data confirm that the Cys and His amino acids are coordinated to metal in the 113Cd adduct. The 3D structure of the zinc adduct [Zn(HIV1-F1)] was determined to high atomic resolution by a new NMR-based approach that utilizes 2D-NOESY back-calculations as a measure of the consistency between the structures and the experimental data. Several interesting structural features were observed, including (1) the presence of extensive internal hydrogen bonding, and (2) the similarity of the folding of the first six residues to the folding observed by X-ray crystallography for related residues in the iron domain of rubredoxin. Structural constraints associated with conservatively substituted glycines provide further rationale for the physiological relevance of the zinc adduct. Similar NMR and structural results have been obtained for the second HIV-1 RT-zinc finger peptide, Zn(HIV1-F2). NMR studies of the zinc adduct with the NCP isolated directly from HIV-1 particles provide solid evidence that zinc finger domains are formed that are conformationally similar (if not identical) to the peptide structures.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
125.
The mechanism(s) by which zinc is transported into cells has not been identified. Since zinc uptake is inhibited by reducing
the temperature, zinc uptake may depend on the movement of plasma membrane micoenvironments, such as endocytosis or potocytosis.
We investigated the potential role of potocytosis in cellular zinc uptake by incubating normal and acrodermatitis enteropathica
fibroblasts with nystatin, a sterol-binding drug previously shown to inhibit potocytosis. Zinc uptake was determined during
initial rates of uptake (10 min) following incubation of the fibroblasts in 50 μg nystatin/mL or 0.1% dimethyl-sulfoxide for
10 min at 37°C. The cells were then incubated with 1 to 30 μM
65zinc. Michaelis-Menten kinetics were observed for zinc uptake. Nystatin inhibited zinc uptake in both the normal and AE fibroblasts.
Reduced cellular uptake of zinc was associated with its internalization, not its external binding. In normal fibroblasts,
nystatin significantly reduced theK
m 56% and theV
max 69%. In the AE fibroblasts, nystatin treatment significantly reduced theV
max 59%, but did not significantly affect theK
m. The AE mutation alone affected theV
max for cellular zinc uptake. The control AE fibroblasts exhibited a 40% reduction inV
max compared to control normal fibroblasts. We conclude that nystatin exerts its effect on zinc uptake by reducing the velocity
at which zinc traverses the cell membrane, possibly through potocytosis. Furthermore, the AE mutation also effects zinc transport
by reducing zinc transport. 相似文献
126.
A crown rot disease in wheat caused by the fungusFusarium graminearum Schw. Group 1 is a widespread problem in chronically Zn-deficient Australian soils. A link between crown rot and Zn deficiency
was established by Sparrow and Graham (1988). This paper reports a test of a further hypothesis, that wheat genotypes more
efficient at extracting zinc from low-zinc soils are more resistant to infection by this pathogen. Three wheat cultivars (Excalibur,
Songlen and Durati) of differential Zn efficiency were tested at three zinc levels (0.05, 0.5 and 2.0 mg Zn kg−1 of soil) and three levels ofF. graminearum S. Group 1 inoculum (0.1 g and 0.3 g kg−1 live chaff-inoculum and control having 0.1 g kg−1 dead chaff inoculum). Six weeks after sowing dry matter production of shoots and roots was decreased byFusarium inoculation at 0.05 mg and 0.5 mg kg−1 applied Zn.Fusarium inoculum at 0.1 g was as effective as 0.3 g kg−1 for infection and decreasing dry matter. The infection at the basal part of culm decreased significantly by increasing the
rate of Zn application. Excalibur, a Zn-efficient cultivar (tolerant to Zn deficiency) produced significantly more shoot and
root dry matter, and showed less disease infection compared with Zn-inefficient cultivars (Durati and Songlen) at low (0.05
mg Zn kg−1 soil) and medium (0.5 mg Zn kg−1 soil) Zn fertilization rates. Higher rate of Zn fertilization (2.0 mg Zn kg−1 soil) reduced the disease level in Durati to the level of Excalibur but the disease level of Songlen was still high, indicating
its high Zn requirement and or sensitivity to crown rot. The data on Zn uptake show that Excalibur, being Zn-efficient, was
able to scavenge enough Zn from Zn-deficient soil, we suggest that besides sustaining growth Excalibur was able to build and
maintain resistance to the pathogen; inefficient cultivars needed extra Zn fertilization to achieve performance comparable
to that of Excalibur. The present study indicates that growing Zn-efficient cultivars of wheat along with judicious use of
Zn fertilizer in Zn-deficient areas where crown rot is a problem may sustain wheat production by reducing the severity of
the disease as well as by increasing the plant vigour through improved Zn nutrition. ei]Section editor: R Rodriques-Kalana 相似文献
127.
128.
Chang FK Sato N Kobayashi-Simorowski N Yoshihara T Meth JL Hamaguchi M 《Journal of molecular biology》2006,364(3):302-308
DBC2 is a tumor suppressor gene linked to breast and lung cancers. Although DBC2 belongs to the RHO GTPase family, it has a unique structure that contains a Broad-Complex/Tramtrack/Bric a Brac (BTB) domain at the C terminus instead of a typical CAAX motif. A limited number of functional studies on DBC2 have indicated its participation in diverse cellular activities, such as ubiquitination, cell-cycle control, cytoskeleton organization and protein transport. In this study, the role of DBC2 in protein transport was analyzed using vesicular stomatitis virus glycoprotein (VSVG) fused with green fluorescent protein. We discovered that DBC2 knockdown hinders the VSVG transport system in 293 cells. Previous studies have demonstrated that VSVG is transported via the microtubule motor complex. We demonstrate that DBC2 mobility depends also on an intact microtubule network. We conclude that DBC2 plays an essential role in microtubule-mediated VSVG transport from the endoplasmic reticulum to the Golgi apparatus. 相似文献
129.
Mutations in SOD1 cause FALS by a gain of function likely related to protein misfolding and aggregation. SOD1 mutations encompass virtually every domain of the molecule, making it difficult to identify motifs important in SOD1 aggregation. Zinc binding to SOD1 is important for structural integrity, and is hypothesized to play a role in mutant SOD1 aggregation. To address this question, we mutated the unique zinc binding sites of SOD1 and examined whether these changes would influence SOD1 aggregation. We generated single and multiple mutations in SOD1 zinc binding residues (H71, H80 and D83) either alone or in combination with an aggregate forming mutation (A4V) known to cause disease. These SOD1 mutants were assayed for their ability to form aggregates.Using an in vitro cellular SOD1 aggregation assay, we show that combining A4V with mutations in non-zinc binding domains (G37R or G85R) increases SOD1 aggregation potential. Mutations at two zinc binding residues (H71G and D83G) also increase SOD1 aggregation potential. However, an H80G mutation at the third zinc binding residue decreases SOD1 aggregation potential even in the context of other aggregate forming SOD1 mutations. These results demonstrate that various mutations have different effects on SOD1 aggregation potential and that the H80G mutation appears to uniquely act as a dominant inhibitor of SOD1 aggregation. 相似文献
130.
The regulatory NEMO (NF-κB essential modulator) protein has a crucial role in the canonical NF-κB signaling pathway notably involved in immune and inflammatory responses, apoptosis and oncogenesis. The regulatory domain is located in the C-terminal half of NEMO and contains a classical CCHC-type zinc finger (ZF). We have investigated the structural and functional effects of a cysteine to phenylalanine point mutation (C417F) in the ZF motif, identified in patients with anhidrotic ectodermal dysplasia with immunodeficiency. The solution structures of the wild type and mutant ZF were determined by NMR. Remarkably, the mutant adopts a global ββα fold similar to that of the wild type and retains thermodynamic stability, i.e., the ability to bind zinc with a native-like affinity, although the last zinc-chelating residue is missing. However, the mutation induces enhanced dynamics in the motif and leads to an important loss of stability. A detailed analysis of the wild type solution structure and experimental evidences led to the identification of two possible protein-binding surfaces that are largely destabilized in the mutant. This is sufficient to alter NEMO function, since functional complementation assays using NEMO-deficient pre-B and T lymphocytes show that full-length C417F pathogenic NEMO leads to a partial to strong defect in LPS, IL-1β and TNF-α-induced NF-κB activation, respectively, as compared to wild type NEMO. Altogether, these results shed light onto the role of NEMO ZF as a protein-binding motif and show that a precise structural integrity of the ZF should be preserved to lead to a functional protein-recognition motif triggering full NF-κB activation. 相似文献