全文获取类型
收费全文 | 2206篇 |
免费 | 278篇 |
国内免费 | 4篇 |
出版年
2021年 | 26篇 |
2020年 | 26篇 |
2018年 | 24篇 |
2017年 | 22篇 |
2016年 | 41篇 |
2015年 | 58篇 |
2014年 | 59篇 |
2013年 | 82篇 |
2012年 | 104篇 |
2011年 | 96篇 |
2010年 | 57篇 |
2009年 | 53篇 |
2008年 | 68篇 |
2007年 | 75篇 |
2006年 | 76篇 |
2005年 | 76篇 |
2004年 | 67篇 |
2003年 | 82篇 |
2002年 | 63篇 |
2001年 | 70篇 |
2000年 | 53篇 |
1999年 | 64篇 |
1998年 | 39篇 |
1997年 | 27篇 |
1996年 | 33篇 |
1995年 | 29篇 |
1994年 | 30篇 |
1993年 | 25篇 |
1992年 | 45篇 |
1991年 | 46篇 |
1990年 | 37篇 |
1989年 | 51篇 |
1988年 | 35篇 |
1987年 | 32篇 |
1986年 | 29篇 |
1985年 | 34篇 |
1984年 | 32篇 |
1983年 | 23篇 |
1982年 | 29篇 |
1979年 | 32篇 |
1978年 | 31篇 |
1977年 | 28篇 |
1976年 | 35篇 |
1975年 | 29篇 |
1974年 | 37篇 |
1973年 | 38篇 |
1971年 | 21篇 |
1970年 | 23篇 |
1969年 | 27篇 |
1968年 | 29篇 |
排序方式: 共有2488条查询结果,搜索用时 265 毫秒
51.
Persistent abnormalities in lipoprotein composition and cholesteryl ester transfer following lovastatin treatment 总被引:3,自引:0,他引:3
J D Bagdade J T Lane N Stone M C Ritter P V Subbaiah 《Journal of lipid research》1990,31(7):1263-1269
Optimally effective lipid-lowering agents should not only restore plasma lipids to normal levels but also correct potentially atherogenic alterations in lipoprotein composition and function often present in hyperlipidemic patients. Lovastatin, a competitive inhibitor of cholesterol biosynthesis, clearly lowers plasma cholesterol levels. Its effects on lipoprotein composition and cholesteryl ester transfer (CET), a key step in reverse cholesterol transport, however, are not known. Since abnormalities in CET and lipoprotein composition are present in patients with hypercholesterolemia, we studied these parameters of plasma lipoprotein transport in twelve hypercholesterolemic (HC; Type IIa) subjects (six male, six female) before and 2 months after lovastatin treatment (20 mg qd). Before lovastatin, the free cholesterol (FC)/lecithin (L) ratio in plasma, a new index of cardiovascular risk that reflects lipoprotein surface composition, was abnormally increased (1.18 +/- 0.26 vs controls 0.83 +/- 0.14; P less than 0.001) in very low density lipoproteins (VLDL) and high density lipoprotein-3 (HDL3), and remained so after treatment despite significant declines in whole plasma cholesterol (311.7 +/- 68.2 vs 215.6 +/- 27.2 mg/dl; P less than 0.001), low density lipoprotein (LDL)-cholesterol (206.3 +/- 47.9 vs 146.8 +/- 29.4; P less than 0.001), and apolipoprotein B (149 +/- 30 vs 110 +/- 17; P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
52.
The paper considers bone-marrow repopulation experiments with injected mixtures of two types, A and B, of genetically marked donor cells. The covariance of the proportions of type A erythrocytes and lymphocytes is analysed as the sum of two components, under a stratified binomial model allowing the proportions of type A cells to vary in postulated strata of the mixture and with the assumption that the genetic marker does not influence cell development. The ratio of the two components is not experimentally estimable, but each of them has an interesting "demographic" interpretation. Possible inferences about certain "two-cell probabilities" are derived, and the experimental findings that necessitated the stratified model are illustrated. 相似文献
53.
Combined subtraction hybridization and polymerase chain reaction amplification procedure for isolation of strain-specific Rhizobium DNA sequences. 总被引:2,自引:0,他引:2 下载免费PDF全文
A novel subtraction hybridization procedure, incorporating a combination of four separation strategies, was developed to isolate unique DNA sequences from a strain of Rhizobium leguminosarum bv. trifolii. Sau3A-digested DNA from this strain, i.e., the probe strain, was ligated to a linker and hybridized in solution with an excess of pooled subtracter DNA from seven other strains of the same biovar which had been restricted, ligated to a different, biotinylated, subtracter-specific linker, and amplified by polymerase chain reaction to incorporate dUTP. Subtracter DNA and subtracter-probe hybrids were removed by phenol-chloroform extraction of a streptavidin-biotin-DNA complex. NENSORB chromatography of the sequences remaining in the aqueous layer captured biotinylated subtracter DNA which may have escaped removal by phenol-chloroform treatment. Any traces of contaminating subtracter DNA were removed by digestion with uracil DNA glycosylase. Finally, remaining sequences were amplified by polymerase chain reaction with a probe strain-specific primer, labelled with 32P, and tested for specificity in dot blot hybridizations against total genomic target DNA from each strain in the subtracter pool. Two rounds of subtraction-amplification were sufficient to remove cross-hybridizing sequences and to give a probe which hybridized only with homologous target DNA. The method is applicable to the isolation of DNA and RNA sequences from both procaryotic and eucaryotic cells. 相似文献
54.
Specificity of binding of beta-glucoside activators of ryegrass (1-->3)-beta-glucan synthase and the synthesis of some potential photoaffinity activators. 下载免费PDF全文
Structure-activity relationships among glycoside activators of ryegrass (Lolium multiflorum) (1-->3)-beta-glucan synthase were investigated using a number of natural and synthetic glycosides, including some carrying photoaffinity functions. There is an absolute requirement for a beta-D-glycosyl moiety in the activator, both S- and N-glucosides are active, and the position of the glucosidic linkage in beta-glucose disaccharides has a significant effect on the affinity of binding. However, the binding requirement does not extend beyond a single beta-D-glucosyl residue, and beta-D-oligoglucosides are less effective than disaccharides. The nature of the aglycon has a major influence on the binding affinity. Hydrophobic aglycons lower the concentration required for half-maximal stimulation of the enzyme obtained from an Eadie-Hofstee plot of kinetic data (Ka) for activation, but charge aglycons increase Ka. Relative to methyl-beta-D-glucoside and cellobiose (Ka 1.1 mM), the most potent compounds tested were N-[4-(benzoyl)benzoyl]-beta-D-glucosylamine and 2'-[4-azidosalicylamino]ethyl-1-thio-beta-D-glucoside with K(a)s of approximately 30 microM. The latter also was tested for its potential to specifically label the beta-glucoside-binding site on the synthase, but under the conditions used the binding was found to be nonspecific. 相似文献
55.
A mutation causing Alport syndrome with tardive hearing loss is common in the western United States. 总被引:5,自引:1,他引:4 下载免费PDF全文
D. F. Barker C. J. Pruchno X. Jiang C. L. Atkin E. M. Stone J. C. Denison P. R. Fain M. C. Gregory 《American journal of human genetics》1996,58(6):1157-1165
Mutations in the COL4A5 gene, located at Xq22, cause Alport syndrome (AS), a nephritis characterized by progressive deterioration of the glomerular basement membrane and usually associated with progressive hearing loss. We have identified a novel mutation, L1649R, present in 9 of 121 independently ascertained families. Affected males shared the same haplotype of eight polymorphic markers tightly linked to COL4A5, indicating common ancestry. Genealogical studies place the birth of this ancestor >200 years ago. The L1649R mutation is a relatively common cause of Alport syndrome in the western United States, in part because of the rapid growth and migratory expansion of mid-nineteenth-century pioneer populations carrying the gene. L1649R affects a highly conserved residue in the NC1 domain, which is involved in key inter- and intramolecular interactions, but results in a relatively mild disease phenotype. Renal failure in an L1649R male typically occurs in the 4th or 5th decade and precedes the onset of significant hearing loss by approximately 10 years. 相似文献
56.
An autosomal recessive nonsyndromic-hearing-loss locus identified by DNA pooling using two inbred Bedouin kindreds. 总被引:5,自引:2,他引:3 下载免费PDF全文
D. A. Scott R. Carmi K. Elbedour S. Yosefsberg E. M. Stone V. C. Sheffield 《American journal of human genetics》1996,59(2):385-391
Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of severe inherited childhood deafness. We present the linkage analysis of two inbred Bedouin kindreds from Israel that are affected with ARNSHL. A rapid genomewide screen for markers linked to the disease was performed by using pooled DNA samples. This screen revealed evidence for linkage with markers D9S922 and D9S301 on chromosome 9q. Genotyping of individuals from both kindreds confirmed linkage to chromosome 9q and a maximum combined LOD score of 26.2 (recombination fraction [theta] .025) with marker D9S927. The disease locus was mapped to a 1.6-cM region of chromosome 9ql3-q2l, between markers D9S15 and D9S927. The disease segregates with a common haplotype in the two kindreds, at markers D9S927, D9S175, and D9S284 in the linked interval, supporting the hypothesis that both kindreds inherited the deafness gene from a common ancestor. Although this nonsyndromic-hearing-loss (NSHL) locus maps to the same cytogenetic interval as DFNB7, it does not overlap the currently defined DFNB7 interval and may represent (1) a novel form of NSHL in close proximity to DFNB7 or (2) a relocalization of the DFNB7 interval to a region telomeric to its reported location. This study further demonstrates that DNA pooling is an effective means of quickly identifying regions of linkage in inbred families with heterogeneous autosomal recessive disorders. 相似文献
57.
BET3 encodes a novel hydrophilic protein that acts in conjunction with yeast SNAREs. 总被引:2,自引:1,他引:1 下载免费PDF全文
G Rossi K Kolstad S Stone F Palluault S Ferro-Novick 《Molecular biology of the cell》1995,6(12):1769-1780
Here we report the identification of BET3, a new member of a group of interacting genes whose products have been implicated in the targeting and fusion of endoplasmic reticulum (ER) to Golgi transport vesicles with their acceptor compartment. A temperature-sensitive mutant in bet3-1 was isolated in a synthetic lethal screen designed to identify new genes whose products may interact with BET1, a type II integral membrane protein that is required for ER to Golgi transport. At 37 degrees C, bet3-1 fails to transport invertase, alpha-factor, and carboxypeptidase Y from the ER to the Golgi complex. As a consequence, this mutant accumulates dilated ER and small vesicles. The SNARE complex, a docking/fusion complex, fails to form in this mutant. Furthermore, BET3 encodes an essential 22-kDa hydrophilic protein that is conserved in evolution, which is not a component of this complex. These findings support the hypothesis that Bet3p may act before the assembly of the SNARE complex. 相似文献
58.
Decay-accelerating factor CD55 is identified as the receptor for echovirus 7 using CELICS, a rapid immuno-focal cloning method. 总被引:14,自引:2,他引:12 下载免费PDF全文
T Ward P A Pipkin N A Clarkson D M Stone P D Minor J W Almond 《The EMBO journal》1994,13(21):5070-5074
Using an anti-receptor mAb that blocks the attachment of echovirus 7 and related viruses (echoviruses 13, 21, 29 and 33), we have isolated a complementary DNA clone that encodes the human decay-accelerating factor (CD55). Mouse cells transfected with the CD55 clone bind echovirus 7, and this binding is blocked by the anti-receptor mAb. The method used (CELICS) allows rapid and direct cloning of genes encoding cell surface receptors. It is based on episomal replication and high efficiency expression of complementary DNA clones in the vector pCDM8 in COS or WOP cells, in conjunction with a sensitive immuno-focal screen that uses antibody probes linked to beta-galactosidase. Receptor positive cells were identified by a colour change and isolated individually using a micromanipulator. DNA extracted from a small number of cells was then cloned directly in Escherichia coli. 相似文献
59.
Stone J 《Bioethics》1994,8(3):223-246
This Paper argues that Living wills are typically nebulous and confused documents that do not effectively enable you to determine your future treatment. Worse, signing a living will can end your life in ways you never intended, long before you are either incompetent or terminally ill. This danger is compounded by the fact that those who implement living wills are often themselves dangerously confused, so that, for example, they cannot be relied upon to distinguish living wills from DNR orders. In addition, the Paper argues that advance directives concerning resuscitation are often so confused that they end the lives of healthy, alert people who have not suffered cardiac or pulmonary arrest. Finally, the paper argues that advance directives establishing durable power of attorney for health care often preserve the chief dangers of living wills. Suggestions are offered as to how you can most effectively direct your future treatment without endangering your life. 相似文献
60.
Peter J. Meikle Nicholas J. Hoogenraad Ingrid Bonig Adrienne E. Clarke Bruce A. Stone 《The Plant journal : for cell and molecular biology》1994,5(1):1-9
Monoclonal antibodies were raised against a (1→3,1→4)-β-glucan-bovine serum albumin (BSA) conjugate. One antibody (BG1) selected for further characterization, was specific for (1→3,1→4)-β-glucan, displaying no binding activity against a (1→3)-β-glucan-BSA conjugate and minimal binding against a cellopentaose-BSA conjugate. A range of oligosaccharides was prepared by enzymatic digestion of (1→3,1→4)-β-glucan, purified by size exclusion chromatography and characterized by 1H-NMR and anion exchange chromatography. These (1→3,1→4)-β-oligoglucosides, together with (1→3)-β- and (1→4)-β-oligoglucosides were used to characterize the binding site of the monoclonal antibody (BG1) by competitive inhibition. The monoclonal antibody showed maximal binding to a heptasaccharide with the structure Glc(1→3) Glc(1→4) Glc(1→4) Glc(1→3) Glc(1→4) Glc(1→4) Glc and was determined to have an affinity constant of 3.8 × 104 M−1 for this oligoglucoside. The monoclonal antibody (BG1) has been used to develop a sensitive sandwich ELISA for the specific quantitation of (1→3,1→4)-β-glucans. The assay operates in the range 1–10 ng ml−1 and shows no significant cross-reaction with tamarind xyloglucan, wheat endosperm arabinoxylan or carboxymethyl-pachyman ((1→3)-β-glucan). When used with a second-stage, rabbit anti-mouse gold conjugate and viewed under the electron microscope, the monoclonal antibody probe was found to bind strongly to the walls of the aleurone in thin sections of immature wheat (Triticum aestivum) cv. Millewa grains but not to the middle lamella region. A previously described specific anti-(1→3)-β-glucan antibody (Meikle et al., 1991) bound to discrete patches on the aleurone walls, believed to be plasmodesmata. 相似文献