全文获取类型
收费全文 | 5314篇 |
免费 | 15篇 |
国内免费 | 32篇 |
专业分类
系统科学 | 31篇 |
丛书文集 | 57篇 |
教育与普及 | 4篇 |
理论与方法论 | 19篇 |
现状及发展 | 2617篇 |
研究方法 | 264篇 |
综合类 | 2300篇 |
自然研究 | 69篇 |
出版年
2017年 | 34篇 |
2012年 | 77篇 |
2011年 | 151篇 |
2008年 | 110篇 |
2007年 | 131篇 |
2006年 | 116篇 |
2005年 | 105篇 |
2004年 | 109篇 |
2003年 | 92篇 |
2002年 | 112篇 |
2001年 | 156篇 |
2000年 | 173篇 |
1999年 | 104篇 |
1992年 | 91篇 |
1991年 | 71篇 |
1990年 | 70篇 |
1989年 | 64篇 |
1988年 | 51篇 |
1987年 | 70篇 |
1986年 | 69篇 |
1985年 | 127篇 |
1984年 | 76篇 |
1983年 | 68篇 |
1982年 | 60篇 |
1981年 | 61篇 |
1980年 | 69篇 |
1979年 | 131篇 |
1978年 | 124篇 |
1977年 | 133篇 |
1976年 | 121篇 |
1975年 | 134篇 |
1974年 | 145篇 |
1973年 | 110篇 |
1972年 | 102篇 |
1971年 | 149篇 |
1970年 | 229篇 |
1969年 | 151篇 |
1968年 | 138篇 |
1967年 | 163篇 |
1966年 | 124篇 |
1965年 | 82篇 |
1964年 | 48篇 |
1962年 | 37篇 |
1959年 | 67篇 |
1958年 | 82篇 |
1957年 | 81篇 |
1956年 | 52篇 |
1955年 | 48篇 |
1954年 | 54篇 |
1948年 | 41篇 |
排序方式: 共有5361条查询结果,搜索用时 125 毫秒
271.
272.
The molecular mechanisms of congenital hypofibrinogenaemia 总被引:7,自引:0,他引:7
Maghzal GJ Brennan SO Homer VM George PM 《Cellular and molecular life sciences : CMLS》2004,61(12):1427-1438
Congenital hypofibrinogenaemia is characterized by abnormally low levels of fibrinogen and is usually caused by heterozygous mutations in the fibrinogen chain genes (, and ). However, it does not usually result in a clinically significant condition unless inherited in a homozygous or compound heterozygous state, where it results in a severe bleeding disorder, afibrinogenaemia. Various protein and expression studies have improved our understanding of how mutations causing hypo- and afibrinogenaemia affect secretion of the mature fibrinogen molecule from the hepatocyte. Some mutations can perturb chain assembly as in the 153 Cys Arg case, while others such as the B Leu Arg and the B414 Gly Ser mutations allow intracellular hexamer assembly but inhibit protein secretion. An interesting group of mutations, such as 284 Gly Arg and 375 Arg Trp, not only cause hypofibrinogenaemia but are also associated with liver disease. The nonexpression of these variant chains in plasma fibrinogen is due to retention in the endoplasmic reticulum, which in turn leads to hypofibrinogenaemia.Received 17 December 2003; received after revision 19 January 2004; accepted 21 January 2004 相似文献
273.
Our understanding of the mode of action of parathyroid hormone-related protein (PTHrP) has changed profoundly during the last decade. Most PTHrP activities are mediated by membrane receptors through autocrine/paracrine pathways. However, both endogenous and exogenous PTHrP also appear to have intracrine effects through translocation into the nucleus. The present review proposes unconventional PTHrP signalling, based on novel clues. First, PTHrP binding to its membrane receptor triggers internalization of the whole complex, mediated by beta-arrestin. There is growing evidence that the receptor and arrestin are the effectors of biological responses, rather than the ligand (or in addition to the ligand). Second, the existence of putative PTHrP targets within the cytoplasm is beginning to be supported. Recent findings of interactions between a COOH-terminus of PTHrP and beta-arrestin and between the PTHrP receptor and 14-3-3 proteins represent the starting point for identification of intracellular partners of both the hormone and its receptor.Received 19 June 2003; received after revision 10 July 2003; accepted 21 July 2003 相似文献
274.
Targeted polymeric micelles for delivery of poorly soluble drugs 总被引:17,自引:0,他引:17
Torchilin VP 《Cellular and molecular life sciences : CMLS》2004,61(19-20):2549-2559
Polymeric micelles (micelles formed by amphiphilic block copolymers) demonstrate a series of attractive properties as drug carriers, such as high stability both in vitro and in vivo and good biocompatibility, and can be successfully used for the solubilization of various poorly soluble pharmaceuticals. These micelles can also be used as targeted drug delivery systems. The targeting can be achieved via the enhanced permeability and retention effect (into the areas with the compromised vasculature), by making micelles of stimuli-responsive amphiphilic block copolymers, or by attaching specific targeting ligand molecules to the micelle surface. Immunomicelles prepared by coupling monoclonal antibody molecules to p-nitrophenylcarbonyl groups on the water-exposed termini of the micelle corona-forming blocks demonstrate high binding specificity and targetability. Immunomicelles prepared with cancer-specific monoclonal antibody 2C5 specifically bind to different cancer cells in vitro and demonstrate increased therapeutic activity in vivo. This new family of pharmaceutical carriers can be used for the solubilization and targeted delivery of poorly soluble drugs to various pathological sites in the body. 相似文献
275.
Tsyba L Rynditch AV Boeri E Jabbari K Bernardi G 《Cellular and molecular life sciences : CMLS》2004,61(6):721-726
The localization of HIV-1 proviruses in compositional DNA fractions from 27 AIDS patients during the chronic phase of the disease with depletion of CD4+ and different levels of viremia showed the following. (1) At low viremia, proviruses are predominantly localized in the GC-richest isochores, which are characterized by an open chromatin structure; this result mimics findings on HIV-1 integration in early infected cells in culture. (2) At higher viremia, an increased distribution of proviruses in GC-poor isochores (which match the GC poorness of HIV-1) was found; this suggests a selection of cells in which the isopycnic localization leads to a higher expression of proviruses and, in turn, to higher viremia. (3) At the highest viremia, integrations in GC-rich isochores are often predominant again, but generally not at the same level as in (1); this may be the consequence of new integrations from the extremely abundant RNA copies.Received 21 November 2003; received after revision 13 January 2004: accepted 15 January 2004 相似文献
276.
Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome 总被引:11,自引:0,他引:11
Ferland RJ Eyaid W Collura RV Tully LD Hill RS Al-Nouri D Al-Rumayyan A Topcu M Gascon G Bodell A Shugart YY Ruvolo M Walsh CA 《Nature genetics》2004,36(9):1008-1013
Joubert syndrome is a congenital brain malformation of the cerebellar vermis and brainstem with abnormalities of axonal decussation (crossing in the brain) affecting the corticospinal tract and superior cerebellar peduncles. Individuals with Joubert syndrome have motor and behavioral abnormalities, including an inability to walk due to severe clumsiness and 'mirror' movements, and cognitive and behavioral disturbances. Here we identified a locus associated with Joubert syndrome, JBTS3, on chromosome 6q23.2-q23.3 and found three deleterious mutations in AHI1, the first gene to be associated with Joubert syndrome. AHI1 is most highly expressed in brain, particularly in neurons that give rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles. Comparative genetic analysis of AHI1 indicates that it has undergone positive evolutionary selection along the human lineage. Therefore, changes in AHI1 may have been important in the evolution of human-specific motor behaviors. 相似文献
277.
278.
Dislocations are line defects that bound plastically deformed regions in crystalline solids. Dislocations terminating on the surface of materials can strongly influence nanostructural and interfacial stability, mechanical properties, chemical reactions, transport phenomena, and other surface processes. While most theoretical and experimental studies have focused on dislocation motion in bulk solids under applied stress and step formation due to dislocations at surfaces during crystal growth, very little is known about the effects of dislocations on surface dynamics and morphological evolution. Here we investigate the near-equilibrium dynamics of surface-terminated dislocations using low-energy electron microscopy. We observe, in real time, the thermally driven nucleation and shape-preserving growth of spiral steps rotating at constant temperature-dependent angular velocities around cores of dislocations terminating on the (111) surface of TiN in the absence of applied external stress or net mass change. We attribute this phenomenon to point-defect migration from the bulk to the surface along dislocation lines. Our results demonstrate that dislocation-mediated surface roughening can occur even in the absence of deposition or evaporation, and provide fundamental insights into mechanisms controlling nanostructural stability. 相似文献
279.
Binding of tetracycline to mammalian spermatozoa 总被引:2,自引:0,他引:2
280.
J. R. Gillette J. V. Dingell F. Sulser R. Kuntzman B. B. Brodie 《Cellular and molecular life sciences : CMLS》1961,17(9):417-418
Zusammenfassung Nach Verabreichung von Imipramin (Tofranil) wurde aus dem Gehirn von Ratten Desmethylimipramin, das N-Monomethylderivat, isoliert. Dieser Metabolit beziehungsweise dessen Anreicherungin vivo scheint für die antidepressive Wirkung von Imipramin verantwortlich zu sein.
Presented in part as an abstract in Fed. Proc.20, 321 (1961). Some of the material in this communication is taken from a dissertation byJ. V. Dingell to be submitted to the Graduate School of Georgetown University in partial fulfillment of the requirements for the degree of Doctor of Philosophy. 相似文献
Presented in part as an abstract in Fed. Proc.20, 321 (1961). Some of the material in this communication is taken from a dissertation byJ. V. Dingell to be submitted to the Graduate School of Georgetown University in partial fulfillment of the requirements for the degree of Doctor of Philosophy. 相似文献