全文获取类型
收费全文 | 1698篇 |
免费 | 123篇 |
国内免费 | 5篇 |
出版年
2023年 | 13篇 |
2022年 | 48篇 |
2021年 | 84篇 |
2020年 | 63篇 |
2019年 | 102篇 |
2018年 | 75篇 |
2017年 | 55篇 |
2016年 | 77篇 |
2015年 | 82篇 |
2014年 | 91篇 |
2013年 | 121篇 |
2012年 | 145篇 |
2011年 | 122篇 |
2010年 | 78篇 |
2009年 | 51篇 |
2008年 | 66篇 |
2007年 | 78篇 |
2006年 | 78篇 |
2005年 | 52篇 |
2004年 | 45篇 |
2003年 | 31篇 |
2002年 | 33篇 |
2001年 | 17篇 |
2000年 | 15篇 |
1999年 | 19篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 7篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 15篇 |
1991年 | 7篇 |
1990年 | 5篇 |
1989年 | 8篇 |
1988年 | 13篇 |
1987年 | 8篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 11篇 |
1983年 | 10篇 |
1982年 | 7篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1974年 | 4篇 |
1973年 | 8篇 |
1972年 | 4篇 |
1969年 | 9篇 |
1968年 | 4篇 |
1967年 | 4篇 |
排序方式: 共有1826条查询结果,搜索用时 31 毫秒
101.
102.
Candida albicans is an opportunistic pathogen. Its proliferation in human hosts is believed to be controlled by immunologic mechanisms. The plasma membrane of the fungus possesses an H(+)-ATPase (PM-ATPase) which actively extrudes protons to generate an electrochemical gradient which is used in co-transport of nutrients. This ATPase is associated with the growth, dimorphism and pathogenicity of the fungus. The physiological concentration of phosphocreatine (PCr) is 20-35 mM in skeletal muscles. H(+)-extrusion in Candida cells was strongly inhibited by PCr; 44% at 20 mM and 69% at 40 mM. H(+)-extrusion was stimulated 6.2-fold in the presence of 10 mM glucose. This glucose stimulated extrusion was inhibited significantly by PCr; 36% at 20 mM and 53% at 40 mM. The intracellular pH pattern of cells destined to differentiate was greatly altered in the presence of PCr. Evagination time for control cells was between 90-120 min. PCr, delayed dimorphism, reduced the population of cells differentiating to hyphae and also reduced the length of hyphae after each time interval. Only 60% differentiation was observed with 10 mM PCr and 40% for higher PCr concentration even after 210 min. Direct interaction of PM-ATPase and PCr has been demonstrated by difference spectrum measurement employing stopped flow spectrophotometer. It can be concluded that PCr may be playing a significant role in checking growth and pathogenesis of C. albicans. 相似文献
103.
Coming to grips with integrin binding to ligands 总被引:1,自引:0,他引:1
Integrins are alphabeta heterodimeric cell-surface receptors that are vital to the survival and function of nucleated cells. They recognize aspartic-acid- or a glutamic-acid-based sequence motifs in structurally diverse ligands. Integrin recognition of most ligands is divalent cation dependent and conformationally sensitive. In addition to this common property, there is an underlying binding specificity between integrins and ligands for which there has been no structural basis. The recently reported crystal structures of the extracellular segment of an integrin in its unliganded state and in complex with a prototypical Arg-Gly-Asp (RGD) ligand have provided an atomic basis for cation-mediated binding of aspartic-acid-based ligands to integrins. They also serve as a basis for modelling other integrins in complex with larger physiologic ligands. These models provide new insights into the molecular basis for ligand binding specificity in integrins and its regulation by activation-driven tertiary and quaternary changes. 相似文献
104.
Ho NH Harapanhalli RS Dahman BA Chen K Wang K Adelstein SJ Kassis AI 《Bioconjugate chemistry》2002,13(2):357-364
We have developed a new strategy that aims to concentrate therapeutic radionuclides within solid tumors. This approach, which we have named EMIT (enzyme-mediated insolubilization therapy), is a method for enzyme-dependent, site-specific, in vivo precipitation of a radioactive molecule (from a water-soluble precursor) within the extracellular space of solid tumors. The prodrug, ammonium 2-(2'-phosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone, labeled with iodine-125 ((125)IPD) and its authentic compound labeled with iodine-127 (IPD) have been synthesized, purified, and characterized. The alkaline phosphatase (ALP)-mediated conversion of these water-soluble nonfluorescent prodrugs to the water-insoluble fluorescent species, iodine-125-labeled 2-(2'-hydroxyphenyl)-6-iodo-4-(3H)-quinazolinone ((125)ID) and its iodine-127-labeled derivative (ID), has been demonstrated in vitro. Biodistribution studies in mice indicate that both (125)IPD and (125)ID are minimally retained by most tissues and organs. In addition, following its intravenous injection in mice, (125)IPD is localized in ALP-rich regions and converted to (125)ID, which remains indefinitely within the tissues where it is produced. We believe that EMIT is a strategy that will lead to the active and specific concentration and entrapment of therapeutic radionuclides within solid tumors, the consequent protracted irradiation of tumor cells within the range of the emitted particles, and the effective therapy of solid tumors. 相似文献
105.
106.
Schiöth HB Bouifrouri AA Rudzish R Muceniece R Watanobe H Wikberg JE Larhammar D 《Regulatory peptides》2002,106(1-3):7-12
The melanocortin 3 and 4 receptors are G-protein-coupled receptors found in the hypothalamus with important role in regulation of the energy balance. In this study, we performed pharmacological comparison of the rat and human melancortin (MC) 3 and MC4 receptors. We transiently expressed the genes for these receptors individually in a mammalian cell line and determined the binding affinities to several MSH peptides. The results showed no major difference between the rat and human MC3 receptors while the rat MC4 receptor had higher affinity to several peptides compared with the human MC4 receptor. NDP-, alpha-, beta-, gamma-MSH, ACTH(1-24), HS014 and MTII had from 5- to 34-fold higher affinity for the rat MC4 receptor, while SHU9119, HS024 and HS028 had similar affinity for both the MC4 receptors. Pharmacological species difference have earlier been reported for the MC1 and MC5 receptors but this is the first report showing important differences between the rat and human MC4 receptors. 相似文献
107.
Lengthening the nose with a tongue-and-groove technique 总被引:2,自引:0,他引:2
Lengthening the short nose is often a major task. The ability to maintain proper alignment between the nasal base and dorsum may prove difficult without sacrificing the suppleness of the former. In this article, the authors introduce a technique of nose lengthening that ensures alignment of the tip with the rest of the nose yet avoids tip rigidity, unless a significant increase in tip projection is also planned. Two spreader grafts are placed, one on either side of the septum, and are extended beyond the caudal septal angle proportional to the planned nasal lengthening. A columella strut, with the cephalocaudal dimension equaling the combination of the width of the existing medial crura plus the amount of planned nasal lengthening, is placed between the medial crura in continuity with the caudal septum and is fixed to the medial crura using 5-0 clear nylon or polydioxanone suture. If additional projection beyond what is achievable by mere placement of a columella strut is required, the strut is fixed to the spreader grafts in a more projected position. Otherwise, the columella strut is simply positioned between the extensions of the spreader grafts. It is necessary to mobilize the lower lateral cartilages to prevent excessive columella show. This procedure has been performed on 23 patients over the past 12.5 years, with 20 patients enjoying good-to-excellent results. The advantages of this technique include its predictability and reproducibility, and the ability to elongate the nose with a mobile nasal base that is in line with the rest of the nose. If suture fixation is used to gain more projection, the technique proves dependable but the nose will become more rigid than is optimal. The requirement of three pieces of properly shaped septal cartilage, which might not be available when a secondary rhinoplasty is performed, is the major disadvantage of this operation. Furthermore, the procedure is, to some degree, labor-intensive. 相似文献
108.
Inhibition of LDL oxidation by flavonoids in relation to their structure and calculated enthalpy 总被引:8,自引:0,他引:8
Vaya J Mahmood S Goldblum A Aviram M Volkova N Shaalan A Musa R Tamir S 《Phytochemistry》2003,62(1):89-99
Twenty flavonoid compounds of five different subclasses were selected, and the relationship of their structure to the inhibition of low-density lipoprotein (LDL) oxidation in vitro was investigated. The most effective inhibitors, by either copper ion or 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) induction, were flavonols and/or flavonoids with two adjacent hydroxyl groups at ring B. In the presence of the later catechol group, the contribution of the double bond and the carbonyl group at ring C was negligible. Isoflavonoids were more effective inhibitors than other flavonoid subclasses with similar structure. Substituting ring B with hydroxyl group(s) at 2' position resulted in a significantly higher inhibitory effect than by substituting ring A or ring B at other positions. The type of LDL inducer had no effect in flavonoids with catechol structure. Calculated heat of formation data (deltadeltaH(f)) revealed that the donation of a hydrogen atom from position 3 was the most likely result, followed by that of a hydroxyl from ring B. Position 3 was favored only in the presence of conjugated double bonds between ring A to ring B. This study makes it possible to assign the contribution of different functional groups among the flavonoid subclasses to in vitro inhibition of LDL oxidation. 相似文献
109.
110.
This study presents chemical syntheses and physical characterization of a new aliphatic poly(L-lactide-b-butylene succinate-b-L-lactide) triblock copolyester with soft and hard biodegradable building blocks. First, poly(butylene succinate) (PBS) prepolymers terminated with hydroxyl functional groups were synthesized through melt polycondensation from succinic acid and 1,4-butanediol. Further, a series of new PLLA-b-PBS-b-PLLA triblock copolyesters bearing various average PLLA block lengths were prepared via ring opening polymerization of L-lactide with the synthesized hydroxyl capped PBS prepolymer (Mn = 4.9 KDa) and stannous octanoate as the macroinitiator and catalyst, respectively. By means of GPC, NMR, FTIR, DSC, TGA, and wide-angle X-ray diffractometer (WAXD), the macromolecular structures and physical properties were intensively studied for these synthesized PBS prepolymer and PLLA-b-PBS-b-PLLA triblock copolyesters. 13C NMR and GPC experimental results confirmed the formation of sequential block structures without any detectable transesterification under the present experimental conditions, and the molecular weights of triblock copolyesters could be readily regulated by adjusting the feeding molar ratio of L-lactide monomer to the PBS macroinitiator. DSC measurements showed all single glass transitions, and their glass transition temperatures were found to be between those of PLLA and PBS, depending on the lengths of PLLA blocks. It was noteworthy that the segmental flexibilities of the hard PLLA blocks were found to be remarkably enhanced by the more flexible PBS block partner, and the PBS and PLLA building blocks were well mixed in the amorphous regions. Results of TGA analyses indicated that thermal degradation and stabilities of the PLLA blocks strongly depended on the average PLLA block lengths of triblock copolyesters. In addition, FTIR and WAXD results showed the coexistence of the assembled PLLA and PBS crystal structures when the average PLLA block length became larger than 7.8. These results may be beneficial for this new biodegradable aliphatic triblock copolyester to be applied as a potential biomaterial. 相似文献