首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1916篇
  免费   245篇
  2021年   14篇
  2017年   18篇
  2016年   21篇
  2015年   34篇
  2014年   46篇
  2013年   70篇
  2012年   84篇
  2011年   94篇
  2010年   43篇
  2009年   44篇
  2008年   87篇
  2007年   91篇
  2006年   81篇
  2005年   54篇
  2004年   76篇
  2003年   75篇
  2002年   68篇
  2001年   82篇
  2000年   63篇
  1999年   50篇
  1998年   33篇
  1997年   27篇
  1996年   26篇
  1995年   31篇
  1994年   30篇
  1993年   31篇
  1992年   34篇
  1991年   56篇
  1990年   52篇
  1989年   39篇
  1988年   39篇
  1987年   31篇
  1986年   28篇
  1985年   37篇
  1984年   35篇
  1983年   31篇
  1982年   23篇
  1981年   25篇
  1980年   18篇
  1979年   31篇
  1978年   26篇
  1977年   18篇
  1976年   17篇
  1975年   24篇
  1974年   23篇
  1973年   19篇
  1972年   24篇
  1971年   11篇
  1969年   13篇
  1967年   11篇
排序方式: 共有2161条查询结果,搜索用时 281 毫秒
71.
The kinetics of refolding of heat-unfolded ribonuclease A have been studied by Fourier transform proton nuclear magnetic resonance at 10 °C, pH 2. A single refolding reaction is observed: it corresponds to the slow-refolding reaction seen in stopped-flow studies of refolding at higher temperatures. There are two results of interest for the mechanism of protein folding. (1) A new resonance (X) is observed that shows the presence of a structural intermediate in refolding. (2) The α-helix close to the N-terminal end of ribonuclease A apparently forms rapidly when the unfolded protein is brought to refolding conditions.The folding intermediate has been studied by monitoring the C-2 protons of the four histidine residues. The intermediate contains one residue (X) in a partly folded environment and the other three residues in unfolded environments. The composite resonance (U) of these three protons at 10 °C agrees with the average chemical shift of the histidine residues in heat-unfolded ribonuclease A at high temperatures. During refolding at 10 °C, the resonance intensities of U and X disappear at the same rate that the spectrum of native ribonuclease A is regained.Partial deuteration experiments show that X is either histidine 12 or 119. Comparative studies of the amino-terminal fragment 1–20 of ribonuclease A indicate that X is histidine 12. The appearance of structure in this peptide can be followed by temperature-dependent changes in the chemical shift of histidine 12. At 10 °C the chemical shifts of histidine 12 and X agree closely. These results are consistent with the circular dichroism study of peptide 1–13 by Brown &; Klec (1971), who concluded that helix formation occurs at low temperatures.  相似文献   
72.
In a retrospective study in women with breast cancer circulating immune complex levels were measured by radioimmunoprecipitation with 125I-Clq. Before operation all the patients showed plasma immune complex levels significantly higher than those in controls. Twelve months after mastectomy patients identified clinicopathologically as having a good prognosis had almost normal levels of immune complexes. By contrast, patients with detectable dissemination on diagnosis or those who died within 22 months after mastectomy had significantly raised plasma levels. The tumour-specific nature of the immune complexes detected remains to be shown and suggestions about the applicability of this test not only for prognosis but also for monitoring the course of malignant diseases need to be confirmed by further investigations.  相似文献   
73.
The peptide Arg.Arg.Leu.Glu.Glu.Glu.Glu.Glu.Ala.Tyr.Gly was synthesized as an analogue of residues 20–30 of human gastrin 34. The epidermal growth factor-stimulated tyrosine kinase of A431 cell membranes phosphorylated the peptide's single tyrosine residue. Km values of 0.11 and 0.61mM and Vmax values of 1.71 and 0.68nmol/min/mg were obtained in the presence and absence of epidermal growth factor respectively. This is the first report of phosphorylation of tyrosine in a sequence related to a human hormone.  相似文献   
74.
75.
Evidence is presented that lactose-fermenting ability (Lac+) in Lactococcus lactis subsp. cremoris AM1, SK11, and ML1 is associated with plasmid DNA, even though these strains are difficult to cure of Lac plasmids. When the Lac plasmids from these strains were introduced into L. lactis subsp. lactis LM0230, they appeared to replicate in a thermosensitive manner; inheritance of the plasmid was less efficient at 32 to 40 degrees C than at 22 degrees C. The stability of the L. lactis subsp. cremoris Lac plasmids in lactococci appeared to be a combination of both host and plasmid functions. Stabilized variants were isolated by growing the cultures at 32 to 40 degrees C; these variants contained the Lac plasmids integrated into the L. lactis subsp. lactis LM0230 chromosome. In addition, the presence of the L. lactis subsp. cremoris Lac plasmids in L. lactis subsp. lactis resulted in a temperature-sensitive growth response; growth of L. lactis subsp. lactis transformants was significantly inhibited at 38 to 40 degrees C, thereby resembling some L. lactis subsp. cremoris strains with respect to temperature sensitivity of growth.  相似文献   
76.
Previous in vivo studies from our laboratory suggested that glucocorticoids antagonize estrogen-dependent actions on LH secretion. This study investigated whether corticosterone (B) may have similar actions on gonadotropin biosynthesis and secretion in vitro. Enzymatically dispersed anterior pituitary cells from adult female rats were cultured for 48 h in alpha-modified Eagle's medium containing 10% steroid-free horse serum with or without 0.5 nM estradiol (E2). The cells were then cultured for 24 h with or without B in the presence or absence of E2. To evaluate hormone release, 5 x 10(5) cells were incubated with varying doses of GnRH (0, 10(-11)-10(-7) M) or pulsatile GnRH (10(-9) M; 20 min/h) for 4 h. Cell and medium LH and FSH were measured by RIA. To evaluate LH biosynthesis, 5 x 10(6) cells were incubated for an additional 24 h with 10(-10) M GnRH, 60 microCi 3H-glucosamine (3H-Gln), 20 microCi 35S-methionine (35S-Met), and the appropriate steroid hormones. Radiolabeled precursor incorporation into LH subunits was determined by immunoprecipitation, followed by SDS-PAGE. Continuous exposure to GnRH stimulated LH release in a dose-dependent manner, and this response was enhanced by E2. B by itself had no effect on LH release, but inhibited LH secretion in E2-primed cells at low concentrations of GnRH (10(-10) M or less). Total LH content was not altered by GnRH or steroid treatment. Similar effects of B were observed in cells that were given a pulsatile GnRH stimulus. In contrast to LH, E2 or B enhanced GnRH-stimulated FSH release at the higher doses of GnRH, while the combination of E2 and B increased basal and further augmented GnRH-stimulated release. Total FSH content was also increased in the presence of B, but not E2 alone, and was further augmented in cells treated with both steroids. There were no effects of the steroids on the magnitude of FSH release in response to GnRH pulses, but the cumulative release of FSH was greater in the E2 + B group compared to controls, indicating an increased basal release. Independent of E2, B suppressed the incorporation of 3H-Gln into LH by more than 50% of control, with only subtle effects on the incorporation of 35S-Met.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   
77.
Analysis of carboxy-terminal peptides derived from endoproteinase Lys-C digests of the scrapie isoform of the hamster prion protein revealed that the majority of the molecules are glycoinositol phospholipid linked through ethanolamine attached at serin-231. However, approximately 15% of PrPSc had a carboxy-terminal peptide that ends at glycine-228. It is intriguing that this glycine is part of the PrP sequence Gly-Arg-Arg, which is an established target sequence for the proteolysis and release of bioactive peptides from larger precursors. The mechanism of formation, as well as the role of the truncated carboxy terminus in the dissemination and neuropathology of scrapie, remains to be determined.  相似文献   
78.
RNA isolated from Chironomus thummi (Diptera) larvae directs the incorporation of amino acid into newly synthesized products in a cell-free translation system prepared from wheat germ. A fraction of the total cell-free product was specifically immunoprecipitable with antibody against total C. thummi hemoglobin. Sodium dodecyl sulfatepolyacrylamide gel electrophoresis of the immunoreactive material revealed the cell-free product to have an apparent molecular mass approximately 3000 daltons greater than secreted C. thummi globin purified from hemolymph. In contrast, analysis of the immunoreactive material by polyacrylamide gel electrophoresis under nondenaturing conditions indicated several chemically distinct globins to be present in the cell-free immunoreactive products. These results provide evidence suggesting the possible existence of a preglobin and the data further provide the initial foundation required for elucidating the regulatory mechanisms that control the developmental stage-specific expression of the globin genes in C. thummi.  相似文献   
79.
80.
The C-peptide of ribonuclease A (residues 1 to 13) is obtained by cyanogen bromide cleavage at Met13, which converts methionine to a mixture of homoserine lactone (giving C-peptide lactone) and homoserine carboxylate (giving C-peptide carboxylate). The helix-forming properties of C-peptide lactone have been reported. The helix is formed intramolecularly in aqueous solution, is stabilized at low temperatures (0 to 20 °C) and also by a pH-dependent interaction between sidechains. The C-peptide lactone helix is about 1000-fold more stable than expected from “host-guest” data for helix formation in synthetic polypeptides.Here we report the failure of C-peptide carboxylate to form an α-helix in comparable conditions. Formation of a salt-bridge between the α-COO? group and the imidazolium ring of His12+ appears to be responsible for the suppression of helix formation. The presence of the Hse13-COO? … His12+ salt-bridge in C-peptide carboxylate is shown by 1H nuclear magnetic resonance titration of the amide proton resonances of His12 and Hse13, and is expected from model peptide studies. The most probable reason why C-peptide carboxylate does not form an α-helix is that the Hse13-COO? … His12+ salt-bridge competes successfully with a helix stabilizing salt-bridge (Glu9? … His12+).S-peptide (residues 1 to 20 of ribonuclease A) does form an α-helix with properties similar to those of the C-peptide (lactone) helix, which shows that the lactone ring of C-peptide lactone is not needed for helix formation.These results support the hypothesis that a Glu9? … His12+ salt-bridge stabilizes the C-peptide (lactone) helix, and they show that specific interactions between side-chains can be important in preventing as well as in promoting α-helix formation.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号