全文获取类型
收费全文 | 429篇 |
免费 | 31篇 |
专业分类
460篇 |
出版年
2020年 | 5篇 |
2019年 | 10篇 |
2018年 | 5篇 |
2016年 | 6篇 |
2015年 | 12篇 |
2014年 | 18篇 |
2013年 | 19篇 |
2012年 | 19篇 |
2011年 | 16篇 |
2010年 | 12篇 |
2009年 | 10篇 |
2008年 | 21篇 |
2007年 | 13篇 |
2006年 | 10篇 |
2005年 | 6篇 |
2004年 | 16篇 |
2003年 | 14篇 |
2002年 | 14篇 |
2001年 | 12篇 |
2000年 | 11篇 |
1999年 | 8篇 |
1998年 | 8篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 11篇 |
1991年 | 6篇 |
1990年 | 8篇 |
1989年 | 9篇 |
1988年 | 12篇 |
1987年 | 8篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1980年 | 4篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1977年 | 9篇 |
1975年 | 12篇 |
1974年 | 9篇 |
1971年 | 3篇 |
1970年 | 5篇 |
1969年 | 5篇 |
1968年 | 5篇 |
1967年 | 4篇 |
1966年 | 4篇 |
1960年 | 3篇 |
排序方式: 共有460条查询结果,搜索用时 8 毫秒
1.
2.
3.
E M Alderman R R Lobb J W Fett J F Riordan J L Bethune B L Vallee 《Biochemistry》1985,24(27):7866-7871
Plasma membranes from the human colon adenocarcinoma cell line HT-29 have been isolated and examined for the presence of angiogenic activity. Membrane-associated macromolecules extracted with Triton X-100 were fractionated on immobilized wheat germ agglutinin. The fraction which bound specifically (about 200 ng of protein/mL packed cells) was highly angiogenic when assayed on the chick embryo chorioallantoic membrane. As little as 0.2 ng of this human tumor derived material consistently induced neovascularization. Similarly, 1-2 ng of this material implanted into the rabbit cornea induced new vessel growth (5-8 mm) within 10 days. The plasma membranes of eight other human tumor lines were examined for angiogenic activity. For each, the wheat germ agglutinin bound material induced neovascularization at the low nanogram level. In contrast, the wheat germ agglutinin bound material derived from purified plasma membranes of two normal human diploid fibroblast cell lines failed to induce an angiogenic response on the chick chorioallantoic membrane, even at microgram levels. 相似文献
4.
Fine-structural alterations in Leishmania tropica within human macrophages exposed to antileishmanial drugs in vitro 总被引:3,自引:0,他引:3
The mechanism of action of antileishmanial compounds is poorly understood. Ultrastructural changes in Leishmania tropica within human macrophages exposed in vitro to Pentostam, pentamidine, amphotericin B, WR 6026, ketoconazole, and Formycin B were examined in these experiments. In Pentostam-treated cultures, some organisms exhibited diminished definition of mitochondrial and other membranes, while other organisms had completely disintegrated. Pentostam-exposed macrophages demonstrated loss of membrane definition in the absence of further alterations; it is therefore hypothesized that impaired macrophage membrane function may contribute towards the effect of this drug against macrophage-contained organisms. Leishmania parasites in pentamidine-treated cultures initially demonstrated swollen kinetoplasts and fragmentation of the kinetoplast DNA core. The initial observed effect of the other four drugs on the parasites was cytoplasmic condensation. These ultrastructural studies suggest that all five non-antimonial drugs may have different mechanisms of action than antimony (Pentostam) against Leishmania. 相似文献
5.
J F Riordan 《Biochemistry》1973,12(20):3915-3923
6.
CO dehydrogenase/acetyl-CoA synthase (CODH/ACS) is one of the four known nickel enzymes. It is a bifunctional protein that
catalyzes the oxidation of CO to CO2 at a nickel iron-sulfur cluster (Cluster C) and a remarkable condensation reaction between a methyl group (donated from a
methylated corrinoid iron-sulfur protein), carbon monoxide, and coenzyme A to form acetyl-CoA at a separate nickel iron-sulfur
cluster (Cluster A). This review focuses on the current understanding of the structure and function of Cluster A and on related
model chemistry. It describes studies that uncovered the first example of a biological organometallic reaction sequence. The
mechanism of acetyl-CoA synthesis includes enzymebound methylnickel, iron-carbonyl, and acylmetal intermediates. Discovery
of the methylnickel species constituted the first example of an alkylnickel species in biology and unveiled a new biological
role for nickel.
Received: 10 April 1996 / Accepted: 4 July 1996 相似文献
7.
The Mg2+ATPase activity of liver plasma membranes decreases markedly with increasing temperature above 30 degrees. This negative temperature dependency is counteracted by the binding of wheat germ agglutinin, concanavalin A, or Ricinus communis agglutinin (at concentrations greater than or equal 0.5 mg/ml) to membranes prior to assay of the enzyme. With one of these lectins bound, the enzyme has a single energy of activation between 20 degrees and 45 degrees. The binding of dimeric succinyl concanavalin A, soybean agglutinin, fucose-binding lectin from Lotus tetragonolobus, or the leucoagglutinin from Phaseolus vulgaris does not alter the temperature dependency of the enzyme. The latter two lectins, however, do prevent the concanavalin A-induced activation of the enzyme at 37 degrees. At saturating substrate concentrations, the enzyme is not inhibited by any of the lectins tested over a wide range of concentrations. Cytochalasin B and colchicine separately or in combination have little influence on the lectin-induced enhancement of enzyme activity. Chlorpromazine and vinblastine sulfate each partially prevent the activation and in combination do so completely. Treatment of the membranes with the detergent Lubrol-PX or phospholipase A prevents activation of the enzyme by concanavalin A. The results are consistent with a restriction by the lectin of an environment which is normally too disordered for maximal enzyme activity above 30 degrees. 相似文献
8.
The blood pressure regulating somatic isozyme of angiotensin-converting enzyme (ACE) consists of two homologous, tandem domains each containing a putative metal-binding motif (HEXXH), while the testis isozyme consists of just a single domain that is identical with the C-terminal half of somatic ACE. Previous metal analyses of somatic ACE have indicated a zinc stoichiometry of 1 mol of Zn2+/mol of ACE and inhibitor-binding studies have found 1 mol of inhibitor bound/mol of enzyme. These and other data have indicated that only one of the two domains of somatic ACE is catalytically active. We have repeated the metal and inhibitor-binding analyses of ACE from various sources and have determined protein concentration by quantitative amino acid analysis on the basis of accurate polypeptide molecular weights that are now available. We find that the somatic isozyme in fact contains 2 mol of Zn2+ and binds 2 mol of lisinopril (an ACE inhibitor) per mol of enzyme, whereas the testis isozyme contains 1 mol of Zn2+ and binds 1 mol of lisinopril. In the case of somatic ACE, the second equivalent of inhibitor binds to a second zinc-containing site as evidenced by the ability of a moderate excess of inhibitor to protect both zinc ions against dissociation. However, active site titration with lisinopril assayed by hydrolysis of furanacryloyl-Phe-Gly-Gly revealed that 1 mol of inhibitor/mol of enzyme abolished the activity of either isozyme, indicating that the principal angiotensin-converting site likely resides in the C-terminal (testicular) domain of somatic ACE and that binding of inhibitor to this site is stronger than to the second site.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
9.
A new technique for the study of the mechanism of enzymes has been developed. An enzyme, modified by an active-site directed reagent, is digested by one or more proteases. The resulting mixture of oligopeptides is then analyzed directly by gas chromatography-mass spectrometry without the use of separation or isolation procedures. A comparison with unmodified enzyme identifies the modified residue as well as quantifies the reaction. This approach has been applied to the identification of Glu-270 in the active site of carboxypeptidase A using a carbodiimide as modification reagent. Studies on the possible incorporation of 18O (from 18O-enriched water) into Glu-270 or other acidic residues near the active site of carboxypeptidase A show that the oxygens of the carboxyl groups of these residues are not exchangeable. 相似文献
10.
Enzymatically active human testis angiotensin-converting enzyme (ACE) was expressed in Chinese hamster ovary (CHO) cells stably transfected with each of three vectors: p omega-ACE contains a full-length testis ACE cDNA under the control of a retroviral promoter; and pLEN-ACEVII and pLEN-ACE6/5, in which full-length and membrane anchor-minus testis ACE cDNAs, respectively, are under the control of the human metallothionein IIA promoter and SV40 enhancer. In every case, active recombinant human testis ACE (hTACE) was secreted in a soluble form into the culture media, up to 2.4 mg/liter in the media of metal-induced, high-producing clones transfected with one of the pLEN vectors. In addition, membrane-bound recombinant enzyme was recovered from detergent extracts of cell pellets of CHO cells transfected with either p omega-ACE or pLEN-ACE-VII. Recombinant converting enzyme was purified to homogeneity by single-step affinity chromatography of conditioned media and detergent-extracted cell pellets in 85 and 70% overall yield, respectively. Purified hTACE from all sources comigrated with the native testis isozyme on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with M(r) approximately 100 kDa. The native and recombinant proteins cross-reacted equally with anti-human kidney ACE antiserum on Western blotting. The catalytic activity of recombinant angiotensin-converting enzyme, in terms of angiotensin I and 2-furanacryloyl-Phe-Gly-Gly hydrolysis, chloride activation, and lisinopril inhibition, was essentially identical to that of the native enzyme. The facile recovery in high yield of fully active hTACE from the media of stably transfected CHO cells provides a suitable system for investigating structure-function relationships in this enzyme. 相似文献