全文获取类型
收费全文 | 1501篇 |
免费 | 168篇 |
出版年
2019年 | 16篇 |
2016年 | 28篇 |
2015年 | 45篇 |
2014年 | 37篇 |
2013年 | 43篇 |
2012年 | 61篇 |
2011年 | 38篇 |
2010年 | 43篇 |
2009年 | 38篇 |
2008年 | 49篇 |
2007年 | 49篇 |
2006年 | 60篇 |
2005年 | 48篇 |
2004年 | 39篇 |
2003年 | 44篇 |
2002年 | 47篇 |
2001年 | 33篇 |
2000年 | 38篇 |
1999年 | 34篇 |
1998年 | 33篇 |
1997年 | 17篇 |
1996年 | 23篇 |
1995年 | 16篇 |
1992年 | 40篇 |
1991年 | 39篇 |
1990年 | 30篇 |
1989年 | 25篇 |
1988年 | 36篇 |
1987年 | 31篇 |
1986年 | 25篇 |
1985年 | 31篇 |
1984年 | 14篇 |
1983年 | 20篇 |
1982年 | 21篇 |
1981年 | 19篇 |
1980年 | 19篇 |
1979年 | 21篇 |
1978年 | 24篇 |
1977年 | 20篇 |
1976年 | 15篇 |
1975年 | 20篇 |
1974年 | 31篇 |
1973年 | 27篇 |
1972年 | 28篇 |
1971年 | 17篇 |
1970年 | 19篇 |
1969年 | 18篇 |
1968年 | 24篇 |
1967年 | 19篇 |
1966年 | 19篇 |
排序方式: 共有1669条查询结果,搜索用时 15 毫秒
51.
D. Daniëlle de Vries Ilse J. de Wijs Gerhard Wolff Uwe-Peter Ketelsen Hans-Hilger Ropers Bernard A. van Oost 《Human genetics》1993,91(1):51-54
A family with myoclonus epilepsy has been described previously as suffering from an X-linked disorder, because at least four males were affected, and only mild and variable symptoms were seen in some female carriers. In this family, we have now identified a mitochondrial AG (8344) heteroplasmic point mutation. This point mutation has been described in families with maternally inherited myoclonus epilepsy and ragged red fibers. The degree of severity of the disorder in the different family members was reflected in the relative quantity of mutated mitochondrial DNA. It is concluded that the mode of inheritance in this family is not X-linked but maternal. 相似文献
52.
Studies on the biology and function of human cytomegalovirus (HCMV) genes have been hampered by the limited number of viral mutants available for genetic analyses. We have developed a simple procedure to generate and enrich for HCMV recombinants. By inserting the bacterial neo gene, encoding neomycin/kanamycin phosphotransferase, into the large HCMV DNA genome using homologous recombination, selectable mutants of this complex herpesvirus were isolated for the first time. The synthesis of Neo from the viral genome was used to effectively enrich for recombinant viruses (re-viruses) in permissive culture cells grown in the presence of Geneticin (G418). A quick assay for Neo activity in infected cells, based on phosphorylation of kanamycin (Km), was used to easily identify viral recombinants in the process of screening and isolation. This procedure, not used previously to identify re-viruses, proved to be very useful for screening of large numbers of HCMV recombinants. Analysis of re-virus by Southern blotting revealed that the insertion of the marker gene had resulted in the expected deletion of the open reading frames, TRL 13/14 and UL 1–5, of HCMV. Re-virus was stable and showed no differences in growth kinetics as compared to wild-type (wt) virus. The insertion of a selectable marker gene into the HCMV genome and identification of viral recombinants by the Km phosphorylation assay, as presented here, provides the rationale for effective generation, enrichment and stable propagation of HCMV mutants. 相似文献
53.
Is hypusine essential for eukaryotic cell proliferation? 总被引:6,自引:0,他引:6
54.
J. Wolff D. L. Sackett L. Knipling 《Protein science : a publication of the Protein Society》1996,5(10):2020-2028
A role for charge-based interactions in protein stability at the monomer or dimer level is well known. We show here that such interactions can also be important for the higher-order structures of microtubule assembly. Alkali metal chlorides increase the rate of polymerization of pure tubulin driven by either taxol or dimethyl sulfoxide. The effect is cation selective, exhibiting a sequence Na+ > K+ > Li+ > Cs+, with optimal concentrations for Na+ at approximately 160 mM. Hofmeister anion effects are additive with these rate stimulations. Sodium is less potent than guanidinium ion stimulation reported previously, but produces a larger fraction of normal microtubules. Alkali metal cations lower the critical concentration by a factor of approximately 2, produce cold reversible polymers whose formation is sensitive to podophyllotoxin inhibition, increase the fraction of polymers present as microtubules from approximately 0.9 to 0.99, and reverse or prevent urea-induced depolymerization of microtubules. In the presence of microtubule-associated proteins, the promotion of polymerization is no longer cation selective. In the polymerization of tubulin S, in which the acidic C termini of both monomers have been cleaved, the cation enhancement is markedly decreased, although selective persists. Because the selectivity sequence is similar to that of the coil/helix transition of polyglutamic acid, we suggest that a major part, although not all, of the cation selective enhancement of polymerization results from shielding of the glutamate-rich C termini of the tubulin monomers. 相似文献
55.
The polyamine-derived amino acid hypusine: its post-translational formation in eIF-5A and its role in cell proliferation 总被引:1,自引:0,他引:1
Myung Hee Park Young Ae Joe Kee Ryeon Kang Young Bok Lee Edith C. Wolff 《Amino acids》1996,10(2):109-121
Summary The unusual amino acid hypusine [N
-(4-amino-2-hydroxybutyl)lysine] is a unique component of one cellular protein, eukaryotic translation initiation factor 5A (eIF-5A, old terminology, eIF-4D). It is formed posttranslationally and exclusively in this protein in two consecutive enzymatic reactions, (i) modification of a single lysine residue of the eIF-5A precursor protein by the transfer of the 4-aminobutyl moiety of the polyamine spermidine to its-amino group to form the intermediate, deoxyhypusine [N
-(4-aminobutyl)lysine] and (ii) subsequent hydroxylation of this intermediate to form hypusine. The amino acid sequences surrounding the hypusine residue are strictly conserved in all eukaryotic species examined, suggesting the fundamental importance of this amino acid throughout evolution. Hypusine is required for the activity of eIF-5Ain vitro. There is strong evidence that hypusine and eIF-5A are vital for eukaryotic cell proliferation. Inactivation of both of the eIF-5A genes is lethal in yeast and the hypusine modification appears to be a requirement for yeast survival (Schnier et al., 1991 [Mol Cell Biol 11: 3105–3114]; Wöhl et al., 1993 [Mol Gen Genet 241: 305–311]). Furthermore, inhibitors of either of the hypusine biosynthetic enzymes, deoxyhypusine synthase or deoxyhypusine hydroxylase, exert strong anti-proliferative effects in mammalian cells, including many human cancer cell lines. These inhibitors hold potential as a new class of anticancer agents, targeting one specific eukaryotic cellular reaction, hypusine biosynthesis. 相似文献
56.
An Ustilago maydis ergosterol biosynthesis mutant (A14) which is partially blocked in sterol 14alpha-demethylase (P45014DM) activity is described. This mutant accumulated the abnormal 14alpha-methyl sterols, eburicol, 14alpha-methylfecosterol, and obtusifoliol, along with significant amounts of ergosterol. Although the A14 mutant grew nearly as well as the wild type, it was impaired in cell extension growth, which indicated a dysfunction in apical cell wall synthesis. The mutant was also found to be hypersensitive to the azole fungicides penconazole and tebuconazole. 相似文献
57.
R. L. Wolff Bernard Comps Anne M. Marpeau Laurent G. Deluc 《Trees - Structure and Function》1997,12(2):113-118
The fatty acid compositions of the seed oils from ten pine species have been established by capillary gas-liquid chromatography
of the methyl esters. With regard to either normal fatty acids or Δ5-olefinic acids, the general pattern of fatty acids did
not differ from that of other pine seed oils reported previously. The main fatty acid was linoleic (9,12–18:2) acid (44.4–57.1%),
followed by either oleic (9–18:1) acid (13.4–24.5%) or pinolenic (5,9,12–18:3) acid (1.5–25.2%). When applying multivariate
analyses to the chemometric data (13 variables) of 49 pine species (ca. 40% of the living pine species), it was possible to
distinguish between several sections: Pinea, Longifolia, Halepensis, Ponderosa-Banksiana, Sylvestris, and Cembra. The latter section was clearly divided into two sub-groups. A few species that presented a low overall content of Δ5-olefinic
acids, and that grow in warm-temperate regions, were isolated from the bulk of other pine species. It is hypothesized that
Δ5-olefinic acids might be related to cold-acclimation.
Received: 5 June 1997 / Accepted: 17 August 1997 相似文献
58.
Immunocytochemistry using antibodies against various molecular forms of the Ca++ and Zn++-binding S100 proteins predominantly labelled astrocytes. However, especially in the neocortex the staining pattern is variable. Methods of tissue preparation have been evaluated with the aim to preserve as much S 100 immunoreactivity as possible. Optimal results were obtained after perfusion fixation with 4–5% aldehydes, 0.1M sodium cacodylate, 0.1% CaCl2, pH 7.3. In such preparations, astrocytes were completely labelled including their lamellar compartments in large parts of the central nervous system. Ca++-withdrawal had adverse affects on S100 immunoreactivity. Cryostat sections treated with EDTA-containing solutions before fixation showed that Ca++-free S100 can apparently not be fixed to the tissue. Perfusion fixatives containing EDTA resulted in inhomogeneous loss of S100 staining, indicating a differential susceptibility of astrocytic subpopulations. A different type of reduction in S100 immunoreactivity occurred around large neocortical blood vessels. Perivascular defects in immunostaining occasionally appeared even after optimal fixation, but could be regularly provoked by mildly acidic fixation (pH 6.6) or prolonged barbiturate anaesthesia. These defects might be based on S100 release into the cerebrospinal fluid. Presumably under none of the conditions studied can the immunoreactivity of all S100-forms and-fractions be completely preserved in the tissue. However, recommendations are presented for optimizing tissue preparation, to the extent that premortal modifications affecting the stainability of astrocytes may be detected by S100 immunohistochemistry in fixed brain tissue. 相似文献
59.
60.