全文获取类型
收费全文 | 16444篇 |
免费 | 1616篇 |
国内免费 | 1443篇 |
专业分类
19503篇 |
出版年
2024年 | 39篇 |
2023年 | 271篇 |
2022年 | 315篇 |
2021年 | 553篇 |
2020年 | 518篇 |
2019年 | 645篇 |
2018年 | 487篇 |
2017年 | 565篇 |
2016年 | 648篇 |
2015年 | 601篇 |
2014年 | 722篇 |
2013年 | 922篇 |
2012年 | 723篇 |
2011年 | 658篇 |
2010年 | 595篇 |
2009年 | 875篇 |
2008年 | 850篇 |
2007年 | 958篇 |
2006年 | 811篇 |
2005年 | 776篇 |
2004年 | 655篇 |
2003年 | 629篇 |
2002年 | 582篇 |
2001年 | 592篇 |
2000年 | 541篇 |
1999年 | 474篇 |
1998年 | 435篇 |
1997年 | 428篇 |
1996年 | 324篇 |
1995年 | 290篇 |
1994年 | 266篇 |
1993年 | 220篇 |
1992年 | 213篇 |
1991年 | 202篇 |
1990年 | 144篇 |
1989年 | 125篇 |
1988年 | 103篇 |
1987年 | 106篇 |
1986年 | 88篇 |
1985年 | 94篇 |
1984年 | 92篇 |
1983年 | 46篇 |
1982年 | 89篇 |
1981年 | 51篇 |
1980年 | 49篇 |
1979年 | 36篇 |
1978年 | 19篇 |
1977年 | 16篇 |
1976年 | 20篇 |
1975年 | 13篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
101.
102.
103.
Andrea Bazzoli David J. Vance Michael J. Rudolph Yinghui Rong Siva Krishna Angalakurthi Ronald T. Toth IV C. Russell Middaugh David B. Volkin David D. Weis John Karanicolas Nicholas J. Mantis 《Proteins》2017,85(11):1994-2008
In this report we investigated, within a group of closely related single domain camelid antibodies (VHHs), the relationship between binding affinity and neutralizing activity as it pertains to ricin, a fast‐acting toxin and biothreat agent. The V1C7‐like VHHs (V1C7, V2B9, V2E8, and V5C1) are similar in amino acid sequence, but differ in their binding affinities and toxin‐neutralizing activities. Using the X‐ray crystal structure of V1C7 in complex with ricin's enzymatic subunit (RTA) as a template, Rosetta‐based homology modeling coupled with energetic decomposition led us to predict that a single pairwise interaction between Arg29 on V5C1 and Glu67 on RTA was responsible for the difference in ricin toxin binding affinity between V1C7, a weak neutralizer, and V5C1, a moderate neutralizer. This prediction was borne out experimentally: substitution of Arg for Gly at position 29 enhanced V1C7's binding affinity for ricin, whereas the reverse (ie, Gly for Arg at position 29) diminished V5C1's binding affinity by >10 fold. As expected, the V5C1R29G mutant was largely devoid of toxin‐neutralizing activity (TNA). However, the TNA of the V1C7G29R mutant was not correspondingly improved, indicating that in the V1C7 family binding affinity alone does not account for differences in antibody function. V1C7 and V5C1, as well as their respective point mutants, recognized indistinguishable epitopes on RTA, at least at the level of sensitivity afforded by hydrogen‐deuterium mass spectrometry. The results of this study have implications for engineering therapeutic antibodies because they demonstrate that even subtle differences in epitope specificity can account for important differences in antibody function. 相似文献
104.
105.
Human embryonic stem cells(hESCs) can self-renew indefinitely and differentiate into all cell types in the human body.Therefore,they are valuable in regenerative medicine,human developmental biology and drug discovery.A number of hESC lines have been derived from the Chinese population, but limited of them are available for research purposes.Here we report the derivation and characterization of two hESC lines derived from human blastocysts of Chinese origin.These hESCs express alkaline phosphatase and hE... 相似文献
106.
Understanding the population structure, population dynamics and processes that give rise to polyploidy and helps to maintain it is central to our knowledge of the evolution of asexual vertebrates. Previous studies revealed high genetic diversity and several reproductive pathways in the southern populations of the Squalius alburnoides hybrid complex. In contrast, lower genetic variability and the associated limited chance of introducing new genetic combinations may threaten the survival of the northern Mondego populations. We analysed the genetic diversity and structure of nine populations of S. alburnoides in the Iberian Peninsula using microsatellite loci to provide further insights on the evolutionary history of this complex. Special attention was given to the less-studied northern populations (Mondego and Douro basins). Marked population structure, a high frequency of private alleles and a high diversity of some biotypes in the Douro basin indicate that some northern populations may not be at high risk of extinction, contrary to what was expected. The genetic diversity found in the northern Douro populations contradicts the general trend of remarkable genetic impoverishment northwards that occurs in other species and regions. The results indicate the possible existence of a glacial refugium in the Rabaçal River, corroborating findings in other species of this region. Historical events seem to have affected the geographical patterns of genetic variability found among and within the northern and southern populations of this complex and contributed to different patterns of genome composition. Therefore, historical events might have a major role in the long-term persistence of some polyploid hybrid taxa. 相似文献
107.
Unravelling the contributions of density‐dependent and density‐independent factors in determining species population dynamics is a challenge, especially if the two factors interact. One approach is to apply stochastic population models to long‐term data, yet few studies have included interactions between density‐dependent and density‐independent factors, or explored more than one type of stochastic population model. However, both are important because model choice critically affects inference on population dynamics and stability. Here, we used a multiple models approach and applied log‐linear and non‐linear stochastic population models to time series (spanning 29 years) on the population growth rates of Blue Tits Cyanistes caeruleus, Great Tits Parus major and Pied Flycatchers Ficedula hypoleuca breeding in two nestbox populations in southern Germany. We focused on the roles of climate conditions and intra‐ and interspecific competition in determining population growth rates. Density dependence was evident in all populations. For Blue Tits in one population and for Great Tits in both populations, addition of a density‐independent factor improved model fit. At one location, Blue Tit population growth rate increased following warmer winters, whereas Great Tit population growth rates decreased following warmer springs. Importantly, Great Tit population growth rate also decreased following years of high Blue Tit abundance, but not vice versa. This finding is consistent with asymmetric interspecific competition and implies that competition could carry over to influence population dynamics. At the other location, Great Tit population growth rate decreased following years of high Pied Flycatcher abundance but only when Great Tit population numbers were low, illustrating that the roles of density‐dependent and density‐independent factors are not necessarily mutually exclusive. The dynamics of this Great Tit population, in contrast to the other populations, were unstable and chaotic, raising the question of whether interactions between density‐dependent and density‐independent factors play a role in determining the (in) stability of the dynamics of species populations. 相似文献
108.
Variance in reproductive success is a major determinant of the degree of genetic drift in a population. While many plants and animals exhibit high variance in their number of progeny, far less is known about these distributions for microorganisms. Here, we used a strain barcoding approach to quantify variability in offspring number among replicate bacterial populations and developed a Bayesian method to infer the distribution of descendants from this variability. We applied our approach to measure the offspring distributions for five strains of bacteria from the genus Streptomyces after germination and growth in a homogenous laboratory environment. The distributions of descendants were heavy‐tailed, with a few cells effectively ‘winning the jackpot’ to become a disproportionately large fraction of the population. This extreme variability in reproductive success largely traced back to initial populations of spores stochastically exiting dormancy, which provided early‐germinating spores with an exponential advantage. In simulations with multiple dormancy cycles, heavy‐tailed distributions of descendants decreased the effective population size by many orders of magnitude and led to allele dynamics differing substantially from classical population genetics models with matching effective population size. Collectively, these results demonstrate that extreme variability in reproductive success can occur even in growth conditions that are far more homogeneous than the natural environment. Thus, extreme variability in reproductive success might be an important factor shaping microbial population dynamics with implications for predicting the fate of beneficial mutations, interpreting sequence variability within populations and explaining variability in infection outcomes across patients. 相似文献
109.
The registration of volumetric structures in real space involves geometric and density transformations that align a target map and a probe map in the best way possible. Many computational docking strategies exist for finding the geometric transformations that superimpose maps, but the problem of finding an optimal density transformation, for the purposes of difference calculations or segmentation, has received little attention in the literature. We report results based on simulated and experimental electron microscopy maps, showing that a single scale factor (gain) may be insufficient when it comes to minimizing the density discrepancy between an aligned target and probe. We propose an affine transformation, with gain and bias, that is parameterized by known surface isovalues and by an interactive centering of the “cancellation peak” in the surface thresholded difference map histogram. The proposed approach minimizes discrepancies across a wide range of interior densities. Owing to having only two parameters, it avoids overfitting and requires only minimal knowledge of the probe and target maps. The linear transformation also preserves phases and relative amplitudes in Fourier space. The histogram matching strategy was implemented in the newly revised volhist tool of the Situs package, version 2.6. 相似文献
110.
基于F—2群体的鸡重要生长性状遗传分析 总被引:13,自引:1,他引:13
采用F-2设计,以丝羽乌骨鸡(C系)为一亲本,分别与农大褐蛋鸡(B系),及法国明星肉鸡(A系)进行正反交,产生了包含A×C,C×A;B×C,C×B4个杂交组合的F2代群体,建立了可用于定位产肉及产蛋等性状QTL的资源群体.基于这一F-2群体,对体重及日增重等性状表型值进行分析,结果显示,亲本间均值差异显著,分离群体变异大,这组性状间有中等或较高的相关,各性状潜在的QTL座位数不超过10,所建资源家系能够满足QTL定位所需的样本数量,达到了预期的效果. 相似文献