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   1202篇
  免费   172篇
  2021年   14篇
  2020年   10篇
  2019年   11篇
  2018年   9篇
  2017年   13篇
  2016年   20篇
  2015年   30篇
  2014年   38篇
  2013年   57篇
  2012年   69篇
  2011年   67篇
  2010年   38篇
  2009年   37篇
  2008年   55篇
  2007年   58篇
  2006年   47篇
  2005年   55篇
  2004年   33篇
  2003年   36篇
  2002年   40篇
  2001年   39篇
  2000年   36篇
  1999年   24篇
  1998年   19篇
  1997年   12篇
  1996年   25篇
  1995年   17篇
  1993年   16篇
  1992年   24篇
  1991年   34篇
  1990年   32篇
  1989年   26篇
  1988年   25篇
  1987年   20篇
  1986年   9篇
  1985年   19篇
  1984年   17篇
  1983年   16篇
  1981年   11篇
  1980年   14篇
  1979年   12篇
  1978年   20篇
  1977年   13篇
  1976年   10篇
  1975年   25篇
  1974年   16篇
  1973年   14篇
  1972年   11篇
  1971年   8篇
  1969年   9篇
排序方式: 共有1374条查询结果,搜索用时 671 毫秒
41.
42.
In mammalian cells, two of the so-called heat shock (hsp) or stress proteins are components of the mitochondria. One of these, hsp 58, is a member of the bacterial GroEL family, whereas the other, glucose-regulated protein (grp) 75, represents a member of the hsp 70 family of stress proteins. Owing to previous studies implicating a role for both the hsp 70 and GroEL families in facilitating protein maturation events, we used the method of native immunoprecipitation to examine whether hsp 58 and grp 75 might interact with other proteins of the mitochondria. In cells pulse-labeled with [35S]-methionine, a significant number of newly synthesized mitochondrial proteins co-precipitated with either hsp 58 or grp 75. Such interactions appeared transient. For example, providing the pulse-labeled cells a subsequent chase period in the absence of radiolabel resulted in a reduction of co-precipitating proteins. If the pulse-chase labeling experiments were performed in the presence of an amino acid analogue, somewhat different results were obtained. Specifically, although many of the newly synthesized and analogue-containing proteins again were observed to co-precipitate with grp 75, the interactions did not appear transient, but instead were stable. Under steady-state labeling conditions, we also observed a portion of hsp 58 and grp 75 in an apparent complex with one another. On addition of ATP, the complex was dissociated. Accompanying this dissociation was the concomitant autophosphorylation of grp 75. On the basis of these observations, as well as previous studies examining the structure/function of the hsp 70 and GroEL proteins, we suspect that both hsp 58 and grp 75 interact with and facilitate the folding and assembly of proteins as they enter into the mitochondria.  相似文献   
43.
In the absence of hormone, human progesterone receptors (PR) are recovered in the cytosolic fraction of cell lysates as a multimeric complex containing the steroid-binding polypeptide, heat shock protein-90 (hsp90), and heat shock protein-70 (hsp70). Activated forms of human PR that acquire the ability to bind to DNA are dissociated from hsp90, but retain association with hsp70. The present study has examined whether associated hsp70 has a function in receptor-DNA binding. When activated PR was bound to specific target DNA in a gel shift assay, no hsp70 was detectable in the PR-DNA complex, as evidenced by the failure of several antibodies to hsp70 to affect the mobility or the amount of complexes. To determine whether hsp70 might indirectly influence DNA-binding activity, we have examined the effect of hsp70 dissociation on PR-DNA-binding activity. Dissociation was achieved either by treatment of immunoaffinity-purified immobilized PR complexes with ATP or by the binding of PR complexes to ATP-agarose, followed by elution with high salt. Under both conditions, dissociation from hsp70 neither enhanced nor impaired the ability of PR to bind to specific DNA. These results suggest that hsp70 is not involved in PR binding to DNA, either directly by participating in DNA binding or indirectly by modulating PR-DNA-binding activity. This implies that hsp70 functions at an earlier stage in the receptor activation pathway. Consistent with the known involvement of hsp70 in stabilizing unfolded states of other target proteins, we propose that hsp70 may assist in nuclear transport of PR or in assembly-disassembly of the 8-10S multimeric complex.  相似文献   
44.
Inhibition of tumor cell invasion by verapamil.   总被引:3,自引:0,他引:3  
Verapamil, a calcium channel antagonist, inhibits murine B16 melanoma and colon adenocarcinoma C26 tumor metastasis by altering platelet aggregation [Tsuruo, T., et al. (1985) Cancer Chemother. Pharmacol., 14:30-33]. However, the role of calcium homeostasis in regulating several biochemical pathways implicated in other steps of the metastatic cascade suggests that calcium channel antagonists could also inhibit metastasis by other mechanisms. In this report, non-toxic doses of verapamil reversibly decreased human A375M and C8161 melanoma cell invasion and metastasis in a dose-dependent manner. Verapamil reduced cellular invasion and metastases by up to 96% (range 78-96%). Concomitantly, verapamil disrupts microtubule and microfilament organization and inhibits unidirectional cell migration but does not affect cellular adhesion to endothelial monolayers or reconstituted basement membranes. In addition, tumor cells treated with verapamil have a decrease in mRNA of type IV collagenase, a proteinase important in tumor cell degradation of basement membranes. Collectively, these data offer additional evidence regarding the mechanisms of action of verapamil as an anti-metastatic agent.  相似文献   
45.
Hair follicle activity and fibre growth were studied using histological sections from the skin of five adult feral does sampled every four weeks for 18 months. The main period of guard hair growth in primary follicles was from November to April. Secondary follicles grew fine, long, nonmedullated fibres (cashmere) from December to June. Shedding of these fibres from secondary follicles had commenced by July and cashmere was absent from the fleece by November. From September to December a subsidiary hair cycle occurred in many secondary follicles which produced minute (vellus) fibres, less than 2.4 mm in length. Some secondary follicles probably shed their cashmere fibres and remain quiescent over spring. Annual pelage changes were therefore achieved with one main growth period, although many secondary follicles underwent another brief hair cycle in spring.  相似文献   
46.
A major drawback to the use in aquaculture of members of the Eubranchiopoda from temporary pool environments is that their eggs do not hatch readily. An investigation of the factors influencing the hatching of eggs of the fairy shrimpStreptocephalus macrourus, showed that light was the only factor of those investigated that was obligatory for hatching. It was found that eggs which had not been desiccated hatched successfully in the presence of absence of adults, while those which had been desiccated showed a block in hatching initially, although this block deteriorated with time and after approximately two months the eggs which had been desiccated showed a similar hatching success to that of the non-desiccated eggs. Exposure of eggs to extremes of heat or cold before incubation did not influence the hatching success of the eggs significantly, but the temperature at which incubation took place was important. The optimal range lay between 14 °C and 20 °C. Eggs hatched and nauplii survived at dissolved oxygen tensions of below 0.5 mg 1–1  相似文献   
47.
Bacteroides fragilis V479-1 (also designated strain 92) has previously been shown to contain a conjugative plasmid, pBF4, that specifies resistance to clindamycin (Cc). A report of inducible tetracycline (Tc) resistance in this strain suggested that this phenotype was also plasmid associated (G. Privitera et al., Nature [London] 278:657-659, 1979) and prompted further investigation. Mating experiments with V469-1 and a Cc-sensitive derivative of V479-1, V598, showed that Tc resistance transfer occurred by a conjugation-like event which was insensitive to DNase, was not mediated by donor culture cell-free filtrates, and required cell-to-cell contact. Results from transfer experiments with V479-1 indicated that Tc and Cc resistance determinants were not linked and segregated independently in matings. Progeny recovered from matings with the V479-1 or V598 donor strain were able to transfer the Tc resistance marker in secondary crosses. Tc resistance transfer from V479-1 or V598 was greatly stimulated by pregrowth in the presence of Tc but not Cc. pBF4-mediated Cc resistance transfer was not affected by pregrowth in the presence of Cc or Tc. Filter blot DNA hybridization studies revealed that pBF4 sequences were not involved in either the Tc resistant phenotype or its associated conjugal transfer properties. The Tc resistance transfer element was not associated with pBF4 or any other extrachromosomal DNA element.  相似文献   
48.
Pseudomonas putida PMD-1 dissimilates naphthalene (Nah), salicylate (Sal), and benzoate (Ben) via catechol which is metabolized through the meta (or alpha-keto acid) pathway. The ability to utilize salicylate but not naphthalene was transferred from P. putida PMD-1 to several Pseudomonas species. Agarose gel electrophoresis of deoxyribonucleic acid (DNA) from PMD-1 and Sal+ exconjugants indicated that a plasmid (pMWD-1) of 110 megadaltons is correlated with the Sal+ phenotype; restriction enzyme analysis of DNA from Sal+ exconjugants indicated that plasmid pMWD-1 was transmitted intact. Enzyme analysis of Sal+ exconjugants demonstrated that the enzymes required to oxidize naphthalene to salicylate are absent, but salicylate hydroxylase and enzymes of the meta pathway are present. Thus, naphthalene conversion to salicylate requires chromosomal genes, whereas salicylate degradation is plasmid encoded. Comparison of restriction digests of plasmid pMWD-1 indicated that it differs considerably from the naphthalene and salicylate degradative plasmids previously described in P. putida.  相似文献   
49.
Physical characterization of Bacteroides fragilis R plasmid pBF4   总被引:23,自引:20,他引:3       下载免费PDF全文
Bacteroides fragilis V479-1 has previously been shown to harbor a self-transmissible 27 X 10(6)-dalton plasmid (pBF4) which confers lincosamide-macrolide resistance. The present study has focused on the physical properties of pBF4. The plasmid was found to be present in 1 to 2 copies per chromosomal equivalent. pBF4 was genetically stable, although spontaneously occurring plasmidless segregants could be detected at low frequency (approximately 1%). This frequency was unaffected by growth of cells in ethidium bromide. About one-third of all spontaneously occurring macrolide-lincosamide-sensitive clones of strain V479-1 were found to contain pBF4 molecules that carried deletions. Ten independently obtained deletion derivatives of pBF4 from lincosamide-macrolide-sensitive strains were compared with the parental pBF4 by restriction endonuclease cleavage analysis. A restriction site map of pBF4 was constructed, and the location of the deletions was approximated. Self-annealed pBF4 molecules, examined by electron microscopy, revealed the presence of two pairs of inverted repeat (IR) sequences on the plasmid. IR-1 was about 400 base pairs in length, and its two component members were separated by an intervening sequence of about 15 kilobases. IR-2 was about 75 base pairs in length, and its component members were separated by 4.2 kilobases. Each of the deletions of pBF4 studied had a terminus at or near the same IR-2 sequence.  相似文献   
50.
The fecal bacterial flora of swine receiving a ration supplemented with chlortetracycline, sulfamethazine, and penicillin was tested for resistance to chlortetracycline and sulfamethazine using anaerobic techniques and medium M-10. Approximately 15.5 and 1.4% of the flora grew in the presence of 25 and 100 microgram of tetracycline/mL, respectively. Higher numbers of bacteria grew in the presence of similar concentrations of sulfamethazine. Thirty-five chlortetracycline-resistant isolates were tentatively identified by genera. Nine different genera were identified, four of these were Gram-positive and five were Gram-negative. The most common genera isolated were Streptococcus and Eubacterium. This demonstrates that in the fecal flora of swine fed rations supplemented with chlortetra-cycline, a wide variety of bacterial genera can be resistant to this antibiotic.  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