全文获取类型
收费全文 | 2242篇 |
免费 | 156篇 |
专业分类
2398篇 |
出版年
2023年 | 4篇 |
2022年 | 25篇 |
2021年 | 30篇 |
2020年 | 16篇 |
2019年 | 33篇 |
2018年 | 60篇 |
2017年 | 42篇 |
2016年 | 80篇 |
2015年 | 112篇 |
2014年 | 96篇 |
2013年 | 161篇 |
2012年 | 196篇 |
2011年 | 190篇 |
2010年 | 121篇 |
2009年 | 112篇 |
2008年 | 148篇 |
2007年 | 129篇 |
2006年 | 107篇 |
2005年 | 109篇 |
2004年 | 122篇 |
2003年 | 103篇 |
2002年 | 121篇 |
2001年 | 13篇 |
2000年 | 9篇 |
1999年 | 4篇 |
1998年 | 22篇 |
1997年 | 14篇 |
1996年 | 17篇 |
1995年 | 15篇 |
1994年 | 12篇 |
1993年 | 17篇 |
1992年 | 18篇 |
1991年 | 12篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 11篇 |
1983年 | 9篇 |
1982年 | 11篇 |
1981年 | 11篇 |
1980年 | 7篇 |
1979年 | 9篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1975年 | 10篇 |
1974年 | 7篇 |
1963年 | 2篇 |
排序方式: 共有2398条查询结果,搜索用时 15 毫秒
11.
Giovanna Cacciapuoti Maria Angela Moretti Sabrina Forte Assunta Brio Laura Camardella Vincenzo Zappia Marina Porcelli 《European journal of biochemistry》2004,271(23-24):4834-4844
The extremely heat-stable 5'-methylthioadenosine phosphorylase from the hyperthermophilic archaeon Pyrococcus furiosus was cloned, expressed to high levels in Escherichia coli, and purified to homogeneity by heat precipitation and affinity chromatography. The recombinant enzyme was subjected to a kinetic analysis including initial velocity and product inhibition studies. The reaction follows an ordered Bi-Bi mechanism and phosphate binding precedes nucleoside binding in the phosphorolytic direction. 5'-Methylthioadenosine phosphorylase from Pyrococcus furiosus is a hexameric protein with five cysteine residues per subunit. Analysis of the fragments obtained after digestion of the protein alkylated without previous reduction identified two intrasubunit disulfide bridges. The enzyme is very resistant to chemical denaturation and the transition midpoint for guanidinium chloride-induced unfolding was determined to be 3.0 M after 22 h incubation. This value decreases to 2.0 M in the presence of 30 mM dithiothreitol, furnishing evidence that disulfide bonds are needed for protein stability. The guanidinium chloride-induced unfolding is completely reversible as demonstrated by the analysis of the refolding process by activity assays, fluorescence measurements and SDS/PAGE. The finding of multiple disulfide bridges in 5'-methylthioadenosine phosphorylase from Pyrococcus furiosus argues strongly that disulfide bond formation may be a significant molecular strategy for stabilizing intracellular hyperthermophilic proteins. 相似文献
12.
13.
Luigi A. M. Castagnetta Orazia M. Granata Vincenzo Bellavia Rosalba Amodio Eugenia Scaccianoce Monica Notarbartolo Maria R. Follari M. Dora Miceli Giuseppe Carruba 《The Journal of steroid biochemistry and molecular biology》1997,61(3-6):287-292
We investigated conversion rates of androgens to estrogens in cultured, hormone-responsive prostate (LNCaP) and breast (MCF-7) human cancer cells. For this purpose, we adopted an intact cell analysis, whereby cells were incubated for different incubation times in the presence of close-to-physiological (1 nM) or supraphysiological (1 μM) concentrations of labelled androgen precursors, i.e. testosterone (T) and androstenedione (Δ4Ad). The aromatase activity, as measured by estrogen formation, was detected in LNCaP cells (0.5 pmol/ml), even though to a significantly lower extent than in MCF-7 cells (5.4 pmol/ml), using 1 μM T after 72 h incubation. Surprisingly, LNCaP cells displayed a much higher aromatase activity when T was used as a substrate with respect to Δ4Ad. In either cell line, T transformation to Δ4Ad was relatively low, attaining only 2.8% in LNCaP and 7.5% MCF-7 cells. However, T was mostly converted to conjugates (over 95%), glucuronides and some sulphates, in LNCaP cells, whereas it was only partly converted to sulphates (<10%) in MCF-7 cells. Aromatase activity seems to be inconsistent in LNCaP cells, being strongly affected by culture conditions, especially by fetal calf serum (FCS). Further studies should assess the regulation of aromatase expression by serum or growth factors in different human cancer cells, also using anti-aromatase and/or anti-estrogen compounds, in different culture conditions. 相似文献
14.
15.
G Licata R Scaglione M A Dichiara G Parrinello G Capuana D Di Vincenzo 《Bollettino della Società italiana di biologia sperimentale》1984,60(10):1863-1869
The authors studied total and free circulating thyroid hormones, rT3, TBG and TSH behaviour on chronic liver disease in 11 subjects with cirrhosis of the liver with ascites(C.E.) and in 6 subjects with chronic active hepatitis (E.C.A.) in comparison with 15 healthy and euthyroid controls. Serum T3,FT3,T4 and FT4 levels were decreased significantly and serum rT3 values increased significantly both in the subjects with C.E. and in patients with E.C.A. Moreover no significantly changes of TSH and TBG levels has been found in 3 groups studied. These data suggest that the alteration of circulating thyroid hormones in chronic liver disease, may represent a compensatory way of reducing the patient's metabolic requirements. 相似文献
16.
Mario De Rosa Salvatore De Rosa Agata Gambacorta Maria Cartenì-Farina Vincenzo Zappia 《The Biochemical journal》1978,176(1):1-7
A spontaneous mutant of Escherichia coli (strain AB2847), selected for resistance to the aminoglycoside antibiotic neamine, shows severe restriction of amber suppressors in vivo. Ribosomes isolated from the mutant exhibit only low misreading in vitro in the presence of the antibiotic. Genetic and biochemical analyses indicate that the neamine-resistant phenotype is the result of two distinct mutations. The first, res3128, appears to affect the gene (strA) coding for the ribosomal protein S12. Although it leads to a restrictive phenotype it does not, however, confer resistance to streptomycin. The second mutation, X3128, is located between the sirA and AROB loci and is lethal when segregated from the res3128 mutation. It may affect the ribosome at the level of a post-translational modification. 相似文献
17.
Ettore Benedetti Benedetto Di Blasio Vincenzo Pavone Carlo Pedone Claudio Toniolo Gian Maria Bonora 《International journal of biological macromolecules》1980,2(4):217-224
The X-ray diffraction and i.r. absorption conformational analysis of has showed the absence of intramolecularly hydrogen-bonded peptide conformations in the solid state. The molecules are held together in rows of ‘cyclic dimer’ motifs through intermolecular NH … OC (acid) and OH … OC {urethane} hydrogen bonds, the secondary amide-like group of the urethane moiety being in the unusual cis conformation, whereas the carboxylic acid group in the common syn conformation. The two molecules in the unit cell present a centrosymmetric set of ?, ψ1, and ψ2 values. In polar solvents solvated species largely predominate. In saturated hydrocarbon solution non-associated and associated (mostly involving the carboxylic acid CO as the proton acceptor) species simultaneously occur. The extent of association decreases with dilution. The amount of intramolecularly hydrogen-bonded oxy-C7 and C5 forms if any, should be extremely small. The type of association at saturation seems to differ from that found in the crystalline compound obtained by precipitation with saturated aliphatic hydrocarbons (from a diethyl ether solution). 相似文献
18.
Champa Sengupta Vincenzo Deluca David S. Bailey Desh Pal S. Verma 《Plant molecular biology》1981,1(1):19-34
The synthesis and processing of the major storage proteins in soybean cotyledons was studied both in vivo and in vitro. The and subunits of 7S as well as the 11S proteins are synthesized as higher molecular weight-precursors on membrane-bound polysomes. The initial translation products of the 7S are proteolytically cleaved during translation suggesting the removal of a signal peptide as evidenced by the presence of 2 and 2 peptides immunoreactive with 7S antibody in the in vitro chain completion products of the membrane-bound polysomes. This is followed or accompanied by cotranslational glycosylation, which increases their size equivalent to that of initially-synthesized precursors. In vivo pulse-labelled 7S and products are of slightly higher molecular weights than the immunoprecipitable chain-completion products, indicating further post-translational modifications. A slow post-translational processing during a period of 1.5 to 16 h yields the final 7S and glycoproteins.Acidic and basic subunits of the 11S protein appear to be synthesized from common large molecular weight (60K-59K) precursors. Antibodies to the 11S acidic component recognize both acidic and basic domains in the precursor while those raised against basic subunits appear to be specific for that region only. The processing of the 11S precursor is also very slow and occurs post-translationally. This slow rate of processing, coupled with a temporal difference in the synthesis of 7S and 11S components, suggests a highly coordinated mechanism for synthesis and packaging of these proteins into protein bodies during seed development. 相似文献
19.
Natale Cascinelli Gian Paolo Balzarini Vincenzo Fontana Sergio Orefice Umberto Veronesi 《Cancer immunology, immunotherapy : CII》1977,2(3):157-161
Summary From November 1973 to December 1974, 20 patients with advanced malignant melanoma were treated with BCG given by intralymphatic route at the Cancer Institute of Milan. The lyophilized Pasteur BCG was used. Patients were treated with a single dose ranging from 0.2–80 mg. Patients' performance status was never severely impaired.The most frequent side effects were fever, lymphangitis, and lymph node enlargement.Variations were observed in white cell count, ERS and immunoglobulins; in no case did we find evidence of liver toxicity or tumor growth enhancement. It is concluded that the intralymphatic route is a safe way of administrating BCG. 相似文献
20.