全文获取类型
收费全文 | 722篇 |
免费 | 42篇 |
出版年
2021年 | 4篇 |
2020年 | 3篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 14篇 |
2015年 | 18篇 |
2014年 | 17篇 |
2013年 | 28篇 |
2012年 | 44篇 |
2011年 | 53篇 |
2010年 | 26篇 |
2009年 | 27篇 |
2008年 | 46篇 |
2007年 | 44篇 |
2006年 | 36篇 |
2005年 | 31篇 |
2004年 | 39篇 |
2003年 | 37篇 |
2002年 | 34篇 |
2001年 | 13篇 |
2000年 | 7篇 |
1999年 | 17篇 |
1998年 | 11篇 |
1997年 | 8篇 |
1996年 | 11篇 |
1995年 | 7篇 |
1994年 | 8篇 |
1993年 | 6篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 5篇 |
1989年 | 11篇 |
1988年 | 11篇 |
1987年 | 10篇 |
1986年 | 6篇 |
1985年 | 9篇 |
1984年 | 9篇 |
1983年 | 6篇 |
1982年 | 11篇 |
1981年 | 12篇 |
1980年 | 9篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1974年 | 4篇 |
1973年 | 6篇 |
1972年 | 3篇 |
1943年 | 3篇 |
1930年 | 2篇 |
1916年 | 3篇 |
排序方式: 共有764条查询结果,搜索用时 31 毫秒
1.
C M Mendel 《Biochimica et biophysica acta》1987,918(2):205-207
A number of studies conducted in the last decade showed that saturable ('specific') binding, by itself, does not necessarily imply biological significance. That is, biological ligands were shown to bind to inert materials as well as to biological receptors in a saturable manner. In these studies specific binding was operationally defined as binding that was displaceable by excess concentrations of unlabeled ligand. This method of measuring specific binding is now no longer considered optimal. To investigate whether optimal (computer-assisted) techniques of measuring specific binding--namely, nonlinear least-squares curve fitting of total binding data, with mathematical separation of the total binding into its various components--might ensure biological significance of measured specific binding, we studied the binding of high-density lipoproteins (HDL3) to tissue culture dishes as an example of binding without biological significance. This binding closely followed the paradigm of a ligand interacting with a class of homogeneous, saturable sites and with a class of relatively unsaturable sites, just as it would have if the HDL3 were interacting with an unpurified biological receptor. This finding indicates that computer-assisted analysis, while most accurately describing binding data, nevertheless does not ensure that measured specific binding has biological significance. Saturability is such a nonselective feature of equilibrium binding data that it should probably no longer be considered one of the criteria for deciding whether or not a defined binding site is a receptor. 相似文献
2.
Xinzhu Deng David Michaelson Jason Tchieu Jin Cheng Diana Rothenstein Regina Feldman Sang-gyu Lee John Fuller Adriana Haimovitz-Friedman Lorenz Studer Simon Powell Zvi Fuks E. Jane Albert Hubbard Richard Kolesnick 《PloS one》2015,10(6)
Mammalian NOTCH1-4 receptors are all associated with human malignancy, although exact roles remain enigmatic. Here we employ glp-1(ar202), a temperature-sensitive gain-of-function C. elegans NOTCH mutant, to delineate NOTCH-driven tumor responses to radiotherapy. At ≤20°C, glp-1(ar202) is wild-type, whereas at 25°C it forms a germline stem cell⁄progenitor cell tumor reminiscent of human cancer. We identify a NOTCH tumor phenotype in which all tumor cells traffic rapidly to G2⁄M post-irradiation, attempt to repair DNA strand breaks exclusively via homology-driven repair, and when this fails die by mitotic death. Homology-driven repair inactivation is dramatically radiosensitizing. We show that these concepts translate directly to human cancer models. 相似文献
3.
A rapid method for cloning and sequencing variable-region genes of expressed immunoglobulins 总被引:9,自引:0,他引:9
A rapid procedure is described for cloning immunoglobulin V region genes from cells that express them. cDNA is synthesized from mRNA template using primers homologous to the immunoglobulin constant-region genes. Blunt-ended, double-stranded cDNA is obtained by sequential addition of enzymes to a single tube. The cDNA is inserted directly into the M13 vector, which is screened by plaque lifting for the presence of specific inserts. Screening probes can be generated from 32P-labeled single-stranded cDNAs generated from primers different from those used for cloning, or alternatively, from previously cloned V or C gene segments. The ease of cloning a cDNA V region is directly related to the abundance of Ig-specific mRNA within the cell of interest. This method minimizes the number of steps and the time needed to obtain accurate and complete sequences of any expressed Ig V region gene. 相似文献
4.
5.
Proenkephalin encodes a group of small peptides with opiate-like activity, the endogenous opioids, known to function as neurohormones, neuromodulators, and neurotransmitters. Recently, we have demonstrated that in addition to its abundance in fetal brain tissue, proenkephalin is highly expressed in nondifferentiated mesodermal cells of developing fetuses. We identified the skeletal tissues, bone, and cartilage as major sites of proenkephalin expression. To examine the possibility that proenkephalin is involved in bone development we have studied the expression of this gene in bone-derived cells, its modulation by bone active hormones, and the effects of enkephalin-derived peptides on osteoblastic phenotype. Our studies revealed that osteoblastic cells synthesize high levels of proenkephalin mRNA which are translated, and the derived peptides are secreted. Reciprocal interrelationships between osteoblast maturation and proenkephalin expression were established. These results together with our observations demonstrating inhibitory effects of proenkephalin-derived peptides on osteoblastic alkaline phosphatase activity, strongly support the notion that proenkephalin is involved in bone development. A different direction of research by other investigators has established the capability of the opioid system in the periphery to participate in the control of pain. On the basis of these two lines of observation, we would like to present the following hypothesis: The potential of embryonic skeletal tissue to synthesize proenkephalin-derived peptides is retained in the adult in small defined undifferentiated cell populations. This potential is realized in certain situations requiring rapid growth, such as remodeling or fracture repair. We suggest that in these processes, similarly to the situation in the embryo, the undifferentiated dividing cells produce the endogenous opioids. In the adult these peptides may have a dual function, namely participating in the control of tissue regeneration and in the control of pain. © 1994 Wiley-Liss, Inc. 相似文献
6.
Summary Physical parameters of membrane bilayers were studied for their effect on the binding of hematoporphyrin derivative (Hpd), which is used as a sensitizer in photodynamic therapy of cancerous tissues. The purpose of this study was to clarify which parameters were relevant, under physiological conditions, to the selectivity of Hpd binding to cancer cells. Fluorescence spectroscopy was used to measure the relative partitioning of the dye between the lipid and aqueous media. Increasing the microviscosity of the liposomes' membranes by various bilayer additives results in a strong reduction of Hpd binding, to an extent independent of the specific additive. The effect of temperature near the physiological value as well as the effect of cross membrane potential are small. Surface potential does not affect the binding constant, indicating that the binding species does not carry a net electric charge. 相似文献
7.
G C Chen D A Hardman R L Hamilton C M Mendel J W Schilling S Zhu K Lau J S Wong J P Kane 《Biochemistry》1989,28(6):2477-2484
The distribution of lipid-binding regions of human apolipoprotein B-100 has been investigated by recombining proteolytic fragments of B-100 with lipids and characterizing the lipid-bound fragments by peptide mapping, amino acid sequencing, and immunoblotting. Fragments of B-100 were generated by digestion of low-density lipoproteins (LDL) in the presence of sodium decyl sulfate with either Staphylococcus aureus V8 protease, pancreatic elastase, or chymotrypsin. Particles with electron microscopic appearance of native lipoproteins formed spontaneously when detergent was removed by dialysis from enzyme digests containing fragments of B-100 and endogenous lipids, or from incubation mixtures of delipidated B-100 fragments mixed with microemulsions of exogenous lipids (cholesteryl oleate and egg phosphatidylcholine). Fractionation of the recombinant particles by isopycnic or density gradient ultracentrifugation yielded complexes similar to native LDL with respect to shape, diameter, electrophoretic mobility, and surface and core compositions. Circular dichroic spectra of these particles showed helicity similar to LDL but a somewhat decreased content of beta-structure. Most of the fragments of B-100 were capable of binding to lipids; 12 were identified by direct sequence analysis and 14 by reaction with antisera against specific sequences within B-100. Our results indicate that lipid-binding regions of B-100 are widely distributed within the protein molecule and that proteolytic fragments derived from B-100 can reassociate in vitro with lipids to form LDL-like particles. 相似文献
8.
Vered Barenholz-Paniry Jacob S. Ishay Zvi Grossman 《Bulletin of mathematical biology》1988,50(6):661-679
Rhythmic “circa-second” contrations of larvae of the hornetVespa orientalis, believed to serve as hunger signals, were studied. A considerable degree of coordination among individual larvae, both in
frequency and phase of these contractions, has been observed. The oscillations of singly isolated larvae are of short duration,
non-constant, with increasing intervals in between and there is a substantial variability in the patterns shown by different
larvae. In contrast, the association of two or more larvae leads to enhancement of their periodic behaviour and to (partial)
entrainment. Communication among larvae may perhaps be mediated by the sound pulses (“scratching” noises) which are generated
by these contractions. We have subjected individual and grouped larvae to external sound pulses and were able to demonstrate:
(a) enhancement of rhythmic activity; (b) phase resetting; (c) entrainment to an external oscillator within a range of frequencies;
(d) the existence of a subharmonic mode of entrainment. We propose a simple phenomenologic model to account for these larvae
responses. Our model assumes the existence of an “energy” variable which declines with time but is upgraded, in a phase-dependent
way, by external stimuli.
Based in part on work performed by V. Barenholz-Paniry in partial fulfillment of the requirements for the M.Sc. degree from
the Sackler Faculty of Medicine, Tel Aviv University, 1986. 相似文献
9.
The activities of nitrite reductase (EC 1.7.7.1) are 60–70% of wild-type activity in pigment-deficient leaves of the chloroplast-ribosomedeficient mutants albostrians (Hordeum vulgare) and iojap (Zea mays). The activity and apoprotein of nitrate reductase (EC 1.6.6.1.) are lacking in the barley mutant. Only very low activities of nitrate reductase can be extracted from leaves of the maize mutant. The molybdenum cofactor of nitrate reductase and xanthine dehydrogenase (EC 1.2.3.2) is present in maize and barley mutant plants. However, it is not inducible by nitrate in pigment-deficient leaves of albostrians. From these results we conclude: (i) Nitrite reductase (a chloroplast enzyme) is synthesized in the cytoplasm and does not need the presence of nitrate reductase for the induction and maintenance if its activity. (ii) The loss or low activity of nitrate reductase is a consequence of the inability of the mutants to accumulate the apoprotein of this enzyme. (iii) The chloroplasts influence the accumulation (i.e. most probably the synthesis) of the nonchloroplast enzyme, nitrate reductase. The accumulation of nitrate reductase needs a chloroplast factor which is not provided by mutant plastids blocked at an early stage of their development.Abbreviations CRM
cross-reacting material
- Mo-co
molybdenum cofactor
- NiR
nitrite reductase
- NR
nitrate reductase 相似文献
10.
CONCOMITANT SYNTHESIS OF MEMBRANE PROTEIN AND EXPORTABLE PROTEIN OF THE SECRETORY GRANULE IN RAT PAROTID GLAND 总被引:10,自引:9,他引:1 下载免费PDF全文
Abraham Amsterdam Michael Schramm Itzhak Ohad Yoram Salomon Zvi Selinger 《The Journal of cell biology》1971,50(1):187-200
After enzyme secretion the membrane of the secretory granule, which had been fused to the cell membrane, was resorbed into the cell. Experiments were therefore carried out to test whether formation of new secretory granules involves reutilization of the resorbed membrane or synthesis of a new membrane, de novo, from amino acids. Incorporation of amino acids-14C into proteins of various cell fractions was measured in vivo, 30, 120, and. 300 min after labeling. At all times the specific radioactivity of the secretory granule membrane was about equal to that of the granule's exportable content. At 120 and 300 min the specific radioactivity of the granule membrane and of the granule content was much higher than that of any other subcellular fraction. It is therefore concluded that the protein of the membrane is synthesized de novo concomitantly with the exportable protein. The proteins of the granule membrane could be distinguished from those of the granule content by gel electrophoresis. All major bands were labeled proportionately to their staining intensity. The amino acid composition of the secretory granule membrane was markedly different from that of the granule's content and also from that of the mitochondrial membrane. The granule membrane showed a high proline content, 30 moles/100 moles amino acids. The analyses show that the radioactivity of the granule membrane is indeed inherent in its proteins and is not due to contamination by other fractions. The possibility is considered that the exportable protein leaves the endoplasmic reticulum already enveloped by the newly synthesized membrane. 相似文献