全文获取类型
收费全文 | 2188篇 |
免费 | 229篇 |
国内免费 | 1篇 |
专业分类
2418篇 |
出版年
2022年 | 27篇 |
2021年 | 62篇 |
2020年 | 39篇 |
2019年 | 48篇 |
2018年 | 61篇 |
2017年 | 38篇 |
2016年 | 72篇 |
2015年 | 103篇 |
2014年 | 108篇 |
2013年 | 118篇 |
2012年 | 141篇 |
2011年 | 140篇 |
2010年 | 79篇 |
2009年 | 98篇 |
2008年 | 114篇 |
2007年 | 101篇 |
2006年 | 106篇 |
2005年 | 85篇 |
2004年 | 77篇 |
2003年 | 78篇 |
2002年 | 62篇 |
2001年 | 38篇 |
2000年 | 31篇 |
1999年 | 36篇 |
1998年 | 19篇 |
1997年 | 11篇 |
1996年 | 16篇 |
1995年 | 11篇 |
1994年 | 10篇 |
1992年 | 26篇 |
1991年 | 28篇 |
1990年 | 25篇 |
1989年 | 36篇 |
1988年 | 22篇 |
1987年 | 17篇 |
1986年 | 33篇 |
1985年 | 16篇 |
1984年 | 20篇 |
1983年 | 24篇 |
1982年 | 12篇 |
1981年 | 13篇 |
1980年 | 18篇 |
1979年 | 20篇 |
1978年 | 15篇 |
1977年 | 12篇 |
1976年 | 17篇 |
1975年 | 13篇 |
1974年 | 15篇 |
1973年 | 18篇 |
1972年 | 22篇 |
排序方式: 共有2418条查询结果,搜索用时 0 毫秒
131.
Hutmacher RB Travis RL Nichols RL Rains DE Roberts BA Weir BL Vargas RM Marsh BH Wright SD Munk DS Munier DJ Keeley MP Fritschi F Delgado RL Perkins S 《TheScientificWorldJournal》2001,1(Z2):691-698
The responses of Acala cotton (Gossypium hirsutum L.) in California to a range of applied nitrogen (N) treatments were investigated in a 5-year, multisite experiment. The experiment's goals were to identify crop growth and yield responses to applied N and provide information to better assess the utility of soil residual N estimates in improving fertilizer management. Baseline fertilizer application rates for the lowest applied N treatments were based on residual soil nitrate-N (NO3-N) levels determined on soil samples from the upper 0.6 m of the soil collected prior to spring N fertilization and within 1 week postplanting each year. Results have shown positive cotton lint yield responses to increases in applied N across the 56 to 224 kg N/ha range in only 41% (16 out of 39) of test sites. Soil NO3-N monitoring to a depth of 2.4 m in the spring (after planting) and fall (postharvest) indicate most changes in soil NO3- occur within the upper 1.2 m of soil. However, some sites (those most prone to leaching losses of soluble nutrients) also exhibited net increases in soil NO3-N in the 1.2- to 2.4-m depth zone when comparing planting time vs. postharvest data. The lack of yield responses and soil NO3-N accumulations at some sites indicate that more efforts should be put into identifying the amount of plant N requirements that can be met from residual soil N, rather than solely from fertilizer N applications. 相似文献
132.
Altering the genetic composition of a population can alter several aspects of its numerical dynamics. Whether natural populations routinely contain the genetic variation capable of affecting the stability of those dynamics is less clear. Here we report a study of experimental populations of mosquitofish (Gambusia holbrooki), designed to examine this issue. The experiment examined the numerical effects of varying the initial relative frequency of a rare male genotype. A higher relative frequency of the rare, melanic genotype produced higher mortality rates in melanic males, higher mortality rates in females, higher juvenile abundance, and fewer fluctuations in the numbers of females across time. This work demonstrates that a natural population can harbour genetic variants in a single gender that are capable of inducing qualitative differences in the numerical dynamics of the opposite gender, through the effects of negative frequency-dependent selection. 相似文献
133.
Populations with high mutation rates (mutator clones) are being found in increasing numbers of species, and a clear link is being established between the presence of mutator clones and drug resistance. Mutator clones exist despite the fact that in a constant environment most mutations are deleterious, with the spontaneous mutation rate generally held at a low value. This implies that mutator clones have an important role in the adaptation of organisms to changing environments. Our study examines how mutator dynamics vary according to the frequency of environmental fluctuations. Although recent studies have considered a single environmental switch, here we investigate mutator dynamics in a regularly varying environment, seeking to mimic conditions present, for example, under certain drug or pesticide regimes. Our model provides four significant new insights. First, the results demonstrate that mutators are most prevalent under intermediate rates of environmental change. When the environment oscillates more rapidly, mutators are unable to provide sufficient adaptability to keep pace with the frequent changes in selection pressure and, instead, a population of 'environmental generalists' dominates. Second, our findings reveal that mutator dynamics may be complex, exhibiting limit cycles and chaos. Third, we demonstrate that when each beneficial mutation provides a greater gain in fitness, mutators achieve higher densities in more rapidly fluctuating environments. Fourth, we find that mutators of intermediate strength reach higher densities than very weak or strong mutators. 相似文献
134.
Enhancing the proteolytic maturation of human immunodeficiency virus type 1 envelope glycoproteins
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Binley JM Sanders RW Master A Cayanan CS Wiley CL Schiffner L Travis B Kuhmann S Burton DR Hu SL Olson WC Moore JP 《Journal of virology》2002,76(6):2606-2616
In virus-infected cells, the envelope glycoprotein (Env) precursor, gp160, of human immunodeficiency virus type 1 is cleaved by cellular proteases into a fusion-competent gp120-gp41 heterodimer in which the two subunits are noncovalently associated. However, cleavage can be inefficient when recombinant Env is expressed at high levels, either as a full-length gp160 or as a soluble gp140 truncated immediately N-terminal to the transmembrane domain. We have explored several methods for obtaining fully cleaved Env for use as a vaccine antigen. We tested whether purified Env could be enzymatically digested with purified protease in vitro. Plasmin efficiently cleaved the Env precursor but also cut at a second site in gp120, most probably the V3 loop. In contrast, a soluble form of furin was specific for the gp120-gp41 cleavage site but cleaved inefficiently. Coexpression of Env with the full-length or soluble form of furin enhanced Env cleavage but also reduced Env expression. When the Env cleavage site (REKR) was mutated in order to see if its use by cellular proteases could be enhanced, several mutants were found to be processed more efficiently than the wild-type protein. The optimal cleavage site sequences were RRRRRR, RRRRKR, and RRRKKR. These mutations did not significantly alter the capacity of the Env protein to mediate fusion, so they have not radically perturbed Env structure. Furthermore, unlike that of wild-type Env, expression of the cleavage site mutants was not significantly reduced by furin coexpression. Coexpression of Env cleavage site mutants and furin is therefore a useful method for obtaining high-level expression of processed Env. 相似文献
135.
Critical role of chromium (Cr)-DNA interactions in the formation of Cr-induced polymerase arresting lesions 总被引:4,自引:0,他引:4
The genotoxicity associated with the metabolic reduction of hexavalent chromium [Cr(VI)] is complex and can impede DNA polymerase-mediated replication in vitro. The exact biochemical nature of Cr-induced polymerase arresting lesions (PALs) is not understood, but is believed to involve the formation of Cr-DNA interstrand cross-links (ICLs). The aim of this investigation was to determine the dependence of direct Cr-DNA interactions on the development of PALs in DNA treated with trivalent Cr [Cr(III)] or with Cr(VI) in the presence of ascorbic acid (Asc), a major intracellular reductant, using an in vitro, acellular system. The formation of Cr-DNA adducts, ICLs, and PALs was maximal at Asc:Cr(VI) molar ratios of 0.5-2, but gradually decreased at higher ratios. EDTA, a Cr(III) chelator, significantly decreased Cr-DNA binding and ICL and PAL formation. Co-treatment of DNA with Cr(VI)/Asc and mannitol, a Cr(V) chelator, selectively inhibited the formation of mono/bifunctional DNA adducts and PALs produced by Cr(VI) reduction, but had no effect on Cr(III)-DNA binding or Cr(III)-induced polymerase arrest. Blocking Cr-DNA phosphate interaction by preincubation of DNA with MgCl(2) abrogated DNA binding and ICL and PAL production. DNA strand breaks and abasic sites may lead to the in vitro arrest of DNA polymerases; however, we failed to detect significant increases in the frequency of these lesions following Cr(VI)/Asc treatment. These data indicate that the bifunctional adduction of Cr to DNA phosphates (ICLs) constitutes a major PAL. Furthermore, the generation of DNA strand breaks and abasic sites by Cr(VI) reduction is insufficient to explain PALs observed in vitro. 相似文献
136.
The first step toward light perception is 11-cis to all-trans photoisomerization of the retinaldehyde chromophore in a rod or cone opsin-pigment molecule. Light sensitivity of the opsin pigment is restored through a multistep pathway called the visual cycle, which effects all-trans to 11-cis re-isomerization of the retinoid chromophore. The maximum throughput of the known visual cycle, however, is too slow to explain sustained photosensitivity in bright light. Here, we demonstrate three novel enzymatic activities in cone-dominant ground-squirrel and chicken retinas: an all-trans-retinol isomerase, an 11-cis-retinyl-ester synthase, and an 11-cis-retinol dehydrogenase. Together these activities comprise a novel pathway that regenerates opsin photopigments at a rate 20-fold faster than the known visual cycle. We suggest that this pathway is responsible for sustained daylight vision in vertebrates. 相似文献
137.
Hennessy MB Voith VL Young TL Hawke JL Centrone J McDowell AL Linden F Davenport GM 《Journal of applied animal welfare science : JAAWS》2002,5(4):253-273
This study examined the effects of 2 manipulations-a brief, regular period of human contact and diet-on the behavior of dogs confined in a public animal shelter. A behavioral battery designed to assess reactions to novel situations, and a test of responsiveness to an unfamiliar human were administered both prior to (pretest) and immediately following (posttest) the 8-week intervention period. Overall, the regular periods of increased human contact together with a diet that contained augmented levels of digestible protein, fat, calories, and animal-derived ingredients reduced signs of behavioral reactivity from pretest to posttest. In some cases, the comparison diet appeared more effective, but only for dogs receiving minimal human interaction. The results indicate that a combination of human interaction and high quality diet may positively affect the behavior of dogs in animal shelters. 相似文献
138.
We assayed several benzamidine derivatives for inhibition potency with HRgpA and RgpB gingipains, enzymes which are involved in the pathogenesis of gingivitis and periodontal disease. The benzamidine derivatives proved to be effective inhibitors of HRgpA and RgpB, with the best inhibitor being a bis-benzamidine with a urea linker (Ki=30 microM). The inhibition potency was increased 2-3 fold in the presence of low concentrations of zinc with the benzamidines containing a urea moiety linking the two aromatic rings. We propose an inhibition model involving a tetrahedral zinc atom coordinated with the active site Cys and His of gingipain and the urea linker in the benzamidine inhibitor. In summary, we have discovered a new series of effective inhibitors for the gingipains and found a novel way to increase inhibitor potency with the HRgpA and RgpB gingipains using zinc. 相似文献
139.
Wong YL Hubieki MP Curfman CL Doncel GF Dudding TC Savle PS Gandour RD 《Bioorganic & medicinal chemistry》2002,10(11):3599-3608
The syntheses of 2-hydroxy-N-(2-hydroxyethyl)-N,N-dimethylhexadecan-1-aminium chloride [1(16)Cl] and iodide [1(16)I], 2-hydroxy-N,N,N-trimethylhexadecan-1-aminium chloride (6), N-(2-hydroxyethyl)-N,N-dimethylhexadecan-1-aminium chloride (8), N,N-bis(2-hydroxyethyl)-N-methylhexadecan-1-aminium chloride (11), and 2-hydroxy-N-(2-hydroxyethyl)-N,N-dimethyl-4-oxahexadecan-1-aminium chloride (14) are reported along with the critical micelle concentrations (cmcs), as measured by conductivity at 25 degrees C, of 1(16)Cl, 1(16)I, 6, 8, 11, and N,N,N-trimethylhexadecan-1-aminium chloride (12). All compounds display spermicidal and virucidal activity. A plot of minimum effective concentration (MEC) in the Sander-Cramer spermicidal assay and cmc shows that 1(16)Cl and 6 have the best spermicidal activity and highest cmcs. Compounds 8, 11, and 1(16)Cl are the most active at 0.05 mg mL(-1) against cell-free and cell-associated virus. In conclusion, 1(16)Cl shows the best combination of dual activity against sperm and HIV; it is a promising candidate for further preclinical studies as a topical, contraceptive microbicide. 相似文献
140.
McBride JM Triplett-McBride T Davie A Newton RU 《Journal of strength and conditioning research / National Strength & Conditioning Association》2002,16(1):75-82
The purpose of this investigation was to examine the effect of an 8-week training program with heavy- vs. light-load jump squats on various physical performance measures and electromyography (EMG). Twenty-six athletic men with varying levels of resistance training experience performed sessions of jump squats with either 30% (JS30, n = 9) or 80% (JS80, n = 10) of their one repetition maximum in the squat (1RM) or served as a control (C, n = 7). An agility test, 20-m sprint, and jump squats with 30% (30J), 55% (55J), and 80% (80J) of their 1RM were performed before and after training. Peak force, peak velocity (PV), peak power (PP), jump height, and average EMG (concentric phase) were calculated for the jumps. There were significant increases in PP and PV in the 30J, 55J, and 80J for the JS30 group (p 相似文献