全文获取类型
收费全文 | 3175篇 |
免费 | 340篇 |
国内免费 | 3篇 |
出版年
2021年 | 30篇 |
2019年 | 26篇 |
2018年 | 32篇 |
2017年 | 31篇 |
2016年 | 64篇 |
2015年 | 87篇 |
2014年 | 107篇 |
2013年 | 151篇 |
2012年 | 157篇 |
2011年 | 154篇 |
2010年 | 100篇 |
2009年 | 110篇 |
2008年 | 135篇 |
2007年 | 134篇 |
2006年 | 157篇 |
2005年 | 149篇 |
2004年 | 145篇 |
2003年 | 126篇 |
2002年 | 116篇 |
2001年 | 53篇 |
2000年 | 35篇 |
1999年 | 57篇 |
1998年 | 40篇 |
1997年 | 35篇 |
1996年 | 41篇 |
1995年 | 52篇 |
1994年 | 53篇 |
1993年 | 54篇 |
1992年 | 64篇 |
1991年 | 48篇 |
1990年 | 48篇 |
1989年 | 47篇 |
1988年 | 34篇 |
1987年 | 41篇 |
1986年 | 55篇 |
1985年 | 59篇 |
1984年 | 50篇 |
1983年 | 28篇 |
1982年 | 31篇 |
1981年 | 35篇 |
1980年 | 29篇 |
1979年 | 43篇 |
1978年 | 30篇 |
1977年 | 25篇 |
1976年 | 27篇 |
1975年 | 19篇 |
1974年 | 24篇 |
1973年 | 25篇 |
1970年 | 33篇 |
1968年 | 19篇 |
排序方式: 共有3518条查询结果,搜索用时 609 毫秒
941.
Li de La Sierra-Gallay I Collinet B Graille M Quevillon-Cheruel S Liger D Minard P Blondeau K Henckes G Aufrère R Leulliot N Zhou CZ Sorel I Ferrer JL Poupon A Janin J van Tilbeurgh H 《Proteins》2004,54(4):776-783
The protein product of the YGR205w gene of Saccharomyces cerevisiae was targeted as part of our yeast structural genomics project. YGR205w codes for a small (290 amino acids) protein with unknown structure and function. The only recognizable sequence feature is the presence of a Walker A motif (P loop) indicating a possible nucleotide binding/converting function. We determined the three-dimensional crystal structure of Se-methionine substituted protein using multiple anomalous diffraction. The structure revealed a well known mononucleotide fold and strong resemblance to the structure of small metabolite phosphorylating enzymes such as pantothenate and phosphoribulo kinase. Biochemical experiments show that YGR205w binds specifically ATP and, less tightly, ADP. The structure also revealed the presence of two bound sulphate ions, occupying opposite niches in a canyon that corresponds to the active site of the protein. One sulphate is bound to the P-loop in a position that corresponds to the position of beta-phosphate in mononucleotide protein ATP complex, suggesting the protein is indeed a kinase. The nature of the phosphate accepting substrate remains to be determined. 相似文献
942.
Belville C Van Vlijmen H Ehrenfels C Pepinsky B Rezaie AR Picard JY Josso N di Clemente N Cate RL 《Molecular endocrinology (Baltimore, Md.)》2004,18(3):708-721
Anti-Müllerian hormone (AMH), a TGF-beta family member, determines whether an individual develops a uterus and Fallopian tubes. Mutations in the AMH gene lead to persistent Müllerian duct syndrome in males. The wild-type human AMH protein is synthesized as a disulfide-linked dimer of two identical 70-kDa polypeptides, which undergoes proteolytic processing to generate a 110-kDa N-terminal dimer and a bioactive 25-kDa TGF-beta-like C-terminal dimer. We have studied the biosynthesis and secretion of wild-type AMH and of seven persistent Müllerian duct syndrome proteins, containing mutations in either the N- or C-terminal domain. Mutant proteins lacking the C-terminal domain are secreted more rapidly than full-length AMH, whereas single amino acid changes in both domains can have profound effects on protein stability and folding. The addition of a cysteine in an N-terminal domain mutant, R194C, prevents proper folding, whereas the elimination of the cysteine involved in forming the interchain disulfide bond, in a C-terminal domain mutant, C525Y, leads to a truncation at the C terminus. A molecular model of the AMH C-terminal domain provides insights into how some mutations could affect biosynthesis and function. 相似文献
943.
Interaction between wall deposition and cell elongation in dark-grown hypocotyl cells in Arabidopsis
A central problem in plant biology is how cell expansion is coordinated with wall synthesis. We have studied growth and wall deposition in epidermal cells of dark-grown Arabidopsis hypocotyls. Cells elongated in a biphasic pattern, slowly first and rapidly thereafter. The growth acceleration was initiated at the hypocotyl base and propagated acropetally. Using transmission and scanning electron microscopy, we analyzed walls in slowly and rapidly growing cells in 4-d-old dark-grown seedlings. We observed thick walls in slowly growing cells and thin walls in rapidly growing cells, which indicates that the rate of cell wall synthesis was not coupled to the cell elongation rate. The thick walls showed a polylamellated architecture, whereas polysaccharides in thin walls were axially oriented. Interestingly, innermost cellulose microfibrils were transversely oriented in both slowly and rapidly growing cells. This suggested that transversely deposited microfibrils reoriented in deeper layers of the expanding wall. No growth acceleration, only slow growth, was observed in the cellulose synthase mutant cesA6(prc1-1) or in seedlings, which had been treated with the cellulose synthesis inhibitor isoxaben. In these seedlings, innermost microfibrils were transversely oriented and not randomized as has been reported for other cellulose-deficient mutants or following treatment with dichlorobenzonitrile. Interestingly, isoxaben treatment after the initiation of the growth acceleration in the hypocotyl did not affect subsequent cell elongation. Together, these results show that rapid cell elongation, which involves extensive remodeling of the cell wall polymer network, depends on normal cellulose deposition during the slow growth phase. 相似文献
944.
Volk DE Thiviyanathan V Rice JS Luxon BA Shah JH Yagi H Sayer JM Yeh HJ Jerina DM Gorenstein DG 《Biochemistry》2003,42(6):1410-1420
The solution structure of an 11-mer DNA duplex, d(CGGTCA*CGAGG) x d(CCTCGTGACCG), containing a 10R adduct at dA* that corresponds to the cis addition of the N(6)-amino group of dA(6) to (+)-(9S,10R)-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene was studied by 2D NMR methods. The NOESY cross-peak patterns indicate that the hydrocarbon is intercalated on the 5'-side of the modified base. This observation is the same as that observed for other oligonucleotides containing (10R)-dA adducts but opposite to that observed for the corresponding (10S)-dA adducts which are intercalated on the 3'-side of the modified base. The hydrocarbon is intercalated from the major groove without significant disruption of either the anti glycosidic torsion angle of the modified residue or the base pairing of the modified residue with the complementary residue on the opposite strand. The ensemble of 10 structures determined exhibits relatively small variations (6-15 degrees) in the characteristic hydrocarbon-base dihedral angles (alpha' and beta') as well as the glycosidic torsion angle chi. These angles are similar to those in a previously determined cis-opened benzo[a]pyrene diol epoxide-(10R)-dA adduct structure. Comparison of the present structure with the cis-opened diol epoxide adduct suggests that the absence of the 7- and 8-hydroxyl groups results in more efficient stacking of the aromatic moiety with the flanking base pairs and deeper insertion of the hydrocarbon into the helix. Relative to normal B-DNA, the duplex containing the present tetrahydroepoxide adduct is unwound at the lesion site, whereas the diol epoxide adduct structure is more tightly wound than normal B-DNA. Buckling of the adducted base pair as well as the C(5)-G(18) base pair that lies immediately above the hydrocarbon is much less severe in the present adducted structure than its cis-opened diol epoxide counterpart. 相似文献
945.
Accumulation of genistein and lipophilic genistein derivatives in lipoproteins during incubation with human plasma in vitro 总被引:1,自引:0,他引:1
Kaamanen M Adlercreutz H Jauhiainen M Tikkanen MJ 《Biochimica et biophysica acta》2003,1631(2):147-152
Atherosclerosis is initiated by the uptake and retention of oxidized low-density lipoprotein (LDL) into the arterial intima. We have previously shown that dietary isoflavone phytoestrogens inhibit LDL oxidation in vitro. The inhibition could have been caused by undetected isoflavone metabolites associated with lipoproteins. In the present study, we incubated human plasma with [3H]genistein, both with and without the lecithin:cholesterol acyltransferase (LCAT) inhibitor dithionitrobenzoic acid (DTNB). Our results indicated that the 3H-label was attached to both high-density lipoprotein (HDL) and LDL, and that it represented both underivatized genistein and lipophilic derivatives of genistein, part of which were identified as fatty acid monoesters. The latter was demonstrated by the findings that DTNB decreased the HDL and LDL associated radioactivity in the lipophilic fraction isolated by hydrophobic chromatography and that saponification hydrolysis liberated a corresponding part of the 3H-label. Two-dimensional reversed-phase thin-layer chromatography (TLC) demonstrated that a corresponding part of the radioactivity comigrated with genistein monoester standards in the absence of DTNB but was abolished if DTNB had been present in the incubation. In summary, incubation of plasma with [3H]genistein resulted in accumulation of underivatized genistein as well as lipophilic genistein derivatives in lipoproteins. A smaller part of the latter were genistein monoesters, while part remained unidentified. Our results suggest an explanation for the increased oxidation resistance of isolated LDL during intake of soybean isoflavones. 相似文献
946.
947.
Maraschin Sde F Lamers GE de Pater BS Spaink HP Wang M 《Journal of experimental botany》2003,54(384):1033-1043
The members of the 14-3-3 isoform family have been shown to be developmentally regulated during animal embryogenesis, where they take part in cell differentiation processes. 14-3-3 isoform-specific expression patterns were studied in plant embryogenic processes, using barley (Hordeum vulgare L.) microspore embryogenesis as a model system. After embryogenesis induction by stress, microspores with enlarged morphology showed higher viability than non-enlarged ones. Following microspore culture, cell division was only observed among the enlarged microspores. Western blot and immunolocalization of three barley 14-3-3 isoforms, 14-3-3A, 14-3-3B and 14-3-3C were carried out using isoform-specific antibodies. The level of 14-3-3C protein was higher in enlarged microspores than in non-enlarged ones. A processed form of 14-3-3A was associated with the death pathway of the non-enlarged microspores. In the early embryogenesis stage, 14-3-3 subcellular localization differed among dividing and non-dividing microspores and the microspore-derived multicellular structures showed a polarized expression pattern of 14-3-3C and a higher 14-3-3A signal in epidermis primordia. In the late embryogenesis stage, 14-3-3C was specifically expressed underneath the L(1) layer of the shoot apical meristem and in the scutellum of embryo-like structures (ELSs). 14-3-3C was also expressed in the scutellum and underneath the L(1) layer of the shoot apical meristem of 21 d after pollination (DAP) zygotic embryos. These results reveal that 14-3-3A processing and 14-3-3C isoform tissue-specific expression are closely related to cell fate and initiation of specific cell type differentiation, providing a new insight into the study of 14-3-3 proteins in plant embryogenesis. 相似文献
948.
Quantitation of soy-derived phytoestrogens in human breast tissue and biological fluids by high-performance liquid chromatography 总被引:6,自引:0,他引:6
Maubach J Bracke ME Heyerick A Depypere HT Serreyn RF Mareel MM De Keukeleire D 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,784(1):137-144
A new and reliable HPLC method for the quantitation of daidzein, equol, and genistein in human breast tissue has been developed. The method was applied to biopsies from women undergoing breast reductions, who, prior to surgery, had ingested either a soy isoflavone preparation or a placebo tablet. The results were compared with data collected for urine and serum of the same subjects using standard methods. The limits of detection in the breast tissue homogenate were 24.7 nmol/l for daidzein, 148.0 nmol/l for equol, and 28.4 nmol/l for genistein (S/N of 3). The chromatographic limits of quantitation were 62.5 nmol/l for daidzein and genistein, and 125.0 nmol/l for equol, for which the accuracies were 86.0%, 83.6%, and 81.8%, respectively. The coefficients of variation of these measurements were all below 20% (11.1% for daidzein, 16.4% for genistein, and 13.2% for equol). The sample preparation comprised a concentration step and the absolute limits of quantitation were, therefore, 4.7 nmol/l, 18.8 nmol/l, and 0.94 nmol/l for daidzein and genistein, and 9.4 nmol/l, 37.5 nmol/l, and 1.9 nmol/l for equol in urine, serum, and breast tissue homogenate, respectively. Recoveries were between 70% (+/-5.6%) in breast tissue homogenate and 100% (+/-14.1%) in urine and serum for all three compounds. Equol (less than 1 micromol/l homogenate) was found to be the predominant phytoestrogen in breast tissue and its concentrations exceeded those in serum. The concentrations of phytoestrogens were at least 100-fold higher in urine than in serum and breast tissue. 相似文献
949.
Nurmi T Voutilainen S Nyyssönen K Adlercreutz H Salonen JT 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,798(1):101-110
Recently new mammalian lignan precursors were identified but no analysis methods are available for assay of those compounds in human urine. Previously published methods were developed for GC-MS about only two plant lignans were included. Consequently, a method for HPLC equipped with a coulometric electrode array detector was developed to measure plant and mammalian lignans in human urine. The plant lignans, secoisolariciresinol (Seco), matairesinol (Mat), lariciresinol (Lar), pinoresinol (Pin), syringaresinol (Syr) and isolariciresinol (IsoL) were included into the new method together with two mammalian lignans, enterolactone (Enl) and enterodiol (End). Validation of the method demonstrated that it could be applied to normal urine containing low amounts of plant lignans and moderate amounts of mammalian lignans, but the method was also applicable for samples from study subjects in supplementation studies, i.e. sample with very high concentrations of mammalian lignans. The method was found to be a useful tool for studies on plant lignan intake and the activity of micro flora in the metabolism of plant lignans. 相似文献
950.
Stalmans I Lambrechts D De Smet F Jansen S Wang J Maity S Kneer P von der Ohe M Swillen A Maes C Gewillig M Molin DG Hellings P Boetel T Haardt M Compernolle V Dewerchin M Plaisance S Vlietinck R Emanuel B Gittenberger-de Groot AC Scambler P Morrow B Driscol DA Moons L Esguerra CV Carmeliet G Behn-Krappa A Devriendt K Collen D Conway SJ Carmeliet P 《Nature medicine》2003,9(2):173-182
Hemizygous deletion of chromosome 22q11 (del22q11) causes thymic, parathyroid, craniofacial and life-threatening cardiovascular birth defects in 1 in 4,000 infants. The del22q11 syndrome is likely caused by haploinsufficiency of TBX1, but its variable expressivity indicates the involvement of additional modifiers. Here, we report that absence of the Vegf164 isoform caused birth defects in mice, reminiscent of those found in del22q11 patients. The close correlation of birth and vascular defects indicated that vascular dysgenesis may pathogenetically contribute to the birth defects. Vegf interacted with Tbx1, as Tbx1 expression was reduced in Vegf164-deficient embryos and knocked-down vegf levels enhanced the pharyngeal arch artery defects induced by tbx1 knockdown in zebrafish. Moreover, initial evidence suggested that a VEGF promoter haplotype was associated with an increased risk for cardiovascular birth defects in del22q11 individuals. These genetic data in mouse, fish and human indicate that VEGF is a modifier of cardiovascular birth defects in the del22q11 syndrome. 相似文献