全文获取类型
收费全文 | 86551篇 |
免费 | 19600篇 |
国内免费 | 5009篇 |
出版年
2024年 | 94篇 |
2023年 | 615篇 |
2022年 | 985篇 |
2021年 | 3251篇 |
2020年 | 3932篇 |
2019年 | 5804篇 |
2018年 | 5828篇 |
2017年 | 5574篇 |
2016年 | 6268篇 |
2015年 | 7477篇 |
2014年 | 7924篇 |
2013年 | 8675篇 |
2012年 | 7462篇 |
2011年 | 6691篇 |
2010年 | 6215篇 |
2009年 | 4557篇 |
2008年 | 4176篇 |
2007年 | 3346篇 |
2006年 | 2992篇 |
2005年 | 2597篇 |
2004年 | 2416篇 |
2003年 | 2191篇 |
2002年 | 1945篇 |
2001年 | 1404篇 |
2000年 | 1222篇 |
1999年 | 1110篇 |
1998年 | 673篇 |
1997年 | 530篇 |
1996年 | 544篇 |
1995年 | 514篇 |
1994年 | 455篇 |
1993年 | 321篇 |
1992年 | 457篇 |
1991年 | 340篇 |
1990年 | 353篇 |
1989年 | 334篇 |
1988年 | 231篇 |
1987年 | 204篇 |
1986年 | 188篇 |
1985年 | 179篇 |
1984年 | 132篇 |
1983年 | 112篇 |
1982年 | 97篇 |
1981年 | 67篇 |
1979年 | 77篇 |
1978年 | 55篇 |
1977年 | 57篇 |
1975年 | 61篇 |
1974年 | 49篇 |
1973年 | 53篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Overexpression of the influenza virus polymerase can titrate out inhibition by the murine Mx1 protein. 下载免费PDF全文
The murine Mx1 protein is an interferon-inducible protein which confers selective resistance to influenza virus infection both in vitro and in vivo. The precise mechanism by which the murine Mx1 specifically inhibits replication of influenza virus is not known. Previously, sensitive replication systems for influenza virus ribonucleoprotein, in which a synthetic influenza virus-like ribonucleoprotein is replicated and transcribed by influenza virus proteins provided in trans, have been developed. With these systems, the antiviral activity of the murine Mx1 protein was examined. It was found that continued expression of influenza polymerase polypeptides via vaccinia virus vectors can titrate out the inhibitory action of the murine Mx1 protein. This titration of inhibitory activity also occurs when the viral PB2 protein alone is overexpressed, suggesting that an antiviral target for the murine Mx1 polypeptide is the viral PB2 protein. 相似文献
992.
Susceptibility of inbred strains of mice to murine AIDS (MAIDS) correlates with target cell expansion and high expression of defective MAIDS virus. 下载免费PDF全文
Murine AIDS (MAIDS) is readily induced by the Duplan strain of defective murine leukemia virus in susceptible C57BL/6 mice. To identify mouse strains resistant to MAIDS, and to understand the genetic factors controlling susceptibility to the disease, we screened more than 20 inbred strains of mice for their susceptibility to MAIDS. For this study, mice of the Fv-1n/n, Fv-1b/b, or Fv-1n/b genotype were inoculated with stocks of defective MAIDS virus pseudotyped with N-tropic, B-tropic, or NB-tropic helper murine leukemia virus, respectively. Strains could be classified as susceptible, resistant, or moderately resistant. None of the individual H-2 haplotypes examined appears to explain resistance to MAIDS by itself. However, a very good correlation between the susceptibility or resistance phenotype and the presence or absence of defective proviral DNA and RNA in the spleen of these animals was found. Since the presence of defective proviral DNA and RNA reflects the oligoclonal proliferation of the cells infected by the defective MAIDS virus, our results strongly suggest that this target cell expansion is genetically controlled and is necessary and perhaps even sufficient for the development of the disease. 相似文献
993.
994.
Virions of primary human immunodeficiency virus type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates. 总被引:55,自引:44,他引:11 下载免费PDF全文
Primary isolates of human immunodeficiency virus type 1 (HIV-1) are much less sensitive to neutralization by soluble CD4 (sCD4) and sCD4-immunoglobulin (Ig) chimeras (CD4-IgG) than are HIV-1 strains adapted to growth in cell culture. We demonstrated that there are significant reductions (10- to 30-fold) in the binding of sCD4 and CD4-IgG to intact virions of five primary isolates compared with sCD4-sensitive, cell culture-adapted isolates RF and IIIB. However, soluble envelope glycoproteins (gp120) derived from the primary isolate virions, directly by detergent solubilization or indirectly by recombinant DNA technology, differed in affinity from RF and IIIB gp120 by only one- to threefold. The reduced binding of sCD4 to these primary isolate virions must therefore be a consequence of the tertiary or quaternary structure of the envelope glycoproteins in their native, oligomeric form on the viral surface. In addition, the rate and extent of sCD4-induced gp120 shedding from these primary isolates was lower than that from RF. We suggest that reduced sCD4 binding and increased gp120 retention together account for the relative resistance of these primary isolates to neutralization by sCD4 and CD4-IgG and that virions of different HIV-1 isolates vary both in the mechanism of sCD4 binding and in subsequent conformational changes in their envelope glycoproteins. 相似文献
995.
996.
A series of glycophospholipids synthesized by coupling mono-, di-, or tri-saccharides to dioleoylphosphatidylethanolamine (DOPE) by reductive amination was used to investigate the interaction of glycophospholipids with phospholipid bilayer membranes. These synthetic glycophospholipids functioned as a stabilizer for the formation of DOPE bilayer vesicles. The minimal mol% of glycophospholipid needed to stabilize the DOPE vesicles were as follows: 8% N-neuraminlactosyl-DOPE (NANL-DOPE), 20% N-maltotriosyl-DOPE (MAT-DOPE), 30% N-lactosyl-DOPE (Lac-DOPE), and 42% N-galactosyl-DOPE (Gal-DOPE). The estimated hydration number of glycophospholipid in reverse micelles was 87, 73, 46, and 14 for NANL-DOPE, MAT-DOPE, Lac-DOPE, and Gal-DOPE, respectively. Thus, the hydration intensity of the glycophospholipid was directly related to the ability to stabilize the DOPE bilayer phase for vesicle formation. Glycophospholipids also reduced the transition temperature from gel to liquid-crystalline phase (Tm) of dipalmitoylphosphatidylcholine (DPPC) bilayers. Interestingly, incorporation of NANL-DOPE induced a decrease of membrane fluidity of DPPC bilayers in the gel phase while other glycophospholipids had no effect. Also, low level of NANL-DOPE but not other glycophospholipids increased the transition temperature (TH) from liquid-crystalline to hexagonal phase of dielaidoylphosphatidylethanolamine bilayers. These results showed that NANL-DOPE with a highly hydratable headgroup which provides a strong stabilization activity for the L alpha phase of phospholipid membranes, may also be involved in specific interactions with neighboring phospholipids via its saccharide moiety. 相似文献
997.
Effect of cationic cholesterol derivatives on gene transfer and protein kinase C activity. 总被引:10,自引:0,他引:10
Four different cationic derivatives of cholesterol were synthesized which contain either a tertiary or a quaternary amino head group, with and without a succinyl spacer-arm. Their ability to inhibit protein kinase C (PKC) activity was measured in a detergent mixed micellar solution. Derivatives containing a quaternary amino head group were effective inhibitors (Ki approx. 12 and 59 microM) of PKC and derivatives containing a tertiary amino head group were approx. 4-20-fold less inhibitory. Liposomes containing an equimolar mixture of dioleoylphosphatidylethanolamine (DOPE) and a cationic cholesterol derivative were tested for the DNA-mediated transfection activity in mouse L929 cells. Highest activity was found with the derivative with low PKC inhibitory activity and with a succinyl spacer-arm. The transfection activity of this tertiary amine derivative, N,N-dimethylethylenediaminyl succinyl cholesterol was dependent on DOPE as a helper lipid; liposomes containing dioleoylphosphatidylcholine and this derivative had little activity. The transfection protocol of this new cationic liposome reagent was optimized with respect to the ratio of liposome/DNA, dose of the complex and time of incubation with cells. Several adherent cell lines could be efficiently transfected with this liposome reagent without any apparent cytotoxicity. However, the transfection activity was strongly inhibited by the presence of serum components. 相似文献
998.
Three B. subitilis serine tRNAs were sequenced including modified nucleosides. All the serine tRNAs contained 1-methyl-adenosine in the D-loop. As other characteristic modified nucleosides, 5-methoxyuridine was found in the first letter of the anticodon in the tRNA(UGA). 相似文献
999.
W K Samson B D Alexander K D Skala F L Huang R J Fulton 《Canadian journal of physiology and pharmacology》1992,70(5):773-778
A variety of neural factors can influence reproductive hormone secretion by neuromodulatory actions within the hypothalamus or neuroendocrine actions within the anterior pituitary gland. Passive immunoneutralization and antagonist administration protocols have suggested physiological roles for a number of these factors; however, both experimental approaches have severe technical limitations. We have developed novel methodology utilizing cytotoxin cell targeting with neuropeptides linked to the toxic A chain of the plant cytotoxin ricin. With this methodology we can target and destroy in vivo or in vitro cells bearing receptors for that peptide. Ricin A chain conjugated to atrial natriuretic peptide (ANP), a neuropeptide known to pharmacologically inhibit luteinizing hormone-releasing hormone (LHRH) release, was injected into the cerebroventricular system of intact, cycling rats and ovariectomized rats. Cytotoxin conjugate treatment significantly lengthened the estrous cycle. In ovariectomized rats the luteinizing hormone surge induced by steroid priming was completely inhibited. LHRH content of the median eminences of these rats was not significantly altered. These data suggest that ANP binding to clearance receptors in the hypothalamus displaces the C-type natriuretic peptide (CNP) from the shared clearance receptor, making more CNP available to inhibit LHRH release. In the absence of cells bearing the clearance receptor all available CNP binds to the ANPR-B receptor and exerts its effect via an inhibitory interneuron, since LHRH fibers are spared by this treatment. 相似文献
1000.
We report here the in vivo conversion of [3H]myoinositol to [3H]chiroinositol. After labeling intraperitoneally with [3H]myoinositol for 3 days to reach radioisotope equilibrium in urine, [3H]chiroinositol was isolated from tissues and purified after 6 N HCl hydrolysis by two sequential paper chromatographies and high performance liquid chromatography (HPLC). Percent conversion of [3H]myoinositol to [3H]chiroinositol was highest in urine (36%), liver (8.8%), muscle (8.8%), and blood (7.6%) with intestine, brain, kidney, spleen, and heart decreasing in percentage from 2.8 to 0.7%. Labeling of other inositol isomers including scyllo-, neo-, and epi-, and mucoinositol was minimal, approximately 0.06% of [3H]myoinositol. Glucose was unlabeled, but glucuronate, the product of myoinositol oxidation, was labeled up to 1.5% of the [3H] myoinositol. Acid hydrolysates of combined inositol-containing phospholipids contain significant labeled chiroinositol. [3H]Phosphatidylinositols and [3H]glycosylphosphatidylinositols were extracted from liver, muscle, and blood, isolated by thin layer chromatography, and inositols purified by HPLC after acid hydrolysis. Percent conversion of [3H]myoinositol to [3H] chiroinositol was highest in blood (60.4%) followed by muscle (7.7%) and liver (2.2%). 相似文献