全文获取类型
收费全文 | 12984篇 |
免费 | 1180篇 |
国内免费 | 785篇 |
专业分类
14949篇 |
出版年
2024年 | 47篇 |
2023年 | 254篇 |
2022年 | 278篇 |
2021年 | 383篇 |
2020年 | 450篇 |
2019年 | 704篇 |
2018年 | 578篇 |
2017年 | 583篇 |
2016年 | 545篇 |
2015年 | 507篇 |
2014年 | 624篇 |
2013年 | 1315篇 |
2012年 | 383篇 |
2011年 | 558篇 |
2010年 | 504篇 |
2009年 | 706篇 |
2008年 | 766篇 |
2007年 | 631篇 |
2006年 | 648篇 |
2005年 | 501篇 |
2004年 | 523篇 |
2003年 | 438篇 |
2002年 | 382篇 |
2001年 | 269篇 |
2000年 | 275篇 |
1999年 | 258篇 |
1998年 | 241篇 |
1997年 | 206篇 |
1996年 | 194篇 |
1995年 | 181篇 |
1994年 | 140篇 |
1993年 | 115篇 |
1992年 | 121篇 |
1991年 | 103篇 |
1990年 | 76篇 |
1989年 | 64篇 |
1988年 | 52篇 |
1987年 | 62篇 |
1986年 | 47篇 |
1985年 | 53篇 |
1984年 | 39篇 |
1983年 | 16篇 |
1982年 | 30篇 |
1981年 | 30篇 |
1980年 | 18篇 |
1979年 | 10篇 |
1978年 | 13篇 |
1977年 | 8篇 |
1976年 | 6篇 |
1973年 | 4篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
21.
A. Galat 《European biophysics journal : EBJ》1990,17(6):331-342
A circular dichroism study was conducted on the solution structure of several different oligonucleotides, whose X-ray structures have been solved. It is suggested that in aqueous solution the oligonucleotides can form structures that maintain geometrical elements which are typical of B-DNA, A-DNA, and their intermediate forms. It is shown that 5'GGATGGGAG:5'CTCCCATCC, which forms an A-DNA helix in the crystal state (McCall et al. 1986), in aqueous solution maintains an A-DNA like structure at temperatures below 10 degrees C. At temperatures between 10 degrees C and 25 degrees C it shows a tendency to form an intermediate structure between A-DNA and B-DNA. Also, it is shown that TFE does not cause a transition from B-DNA to A-DNA helix in short DNA fragments, but instead disrupts the helix. 相似文献
22.
23.
Molecular dynamics simulations were carried out on an insulin crosslinked between the N-terminal A chain and the C-terminal B chain to form a so-called mini-proinsulin: N
-A1-N
-B29-diaminosuberoyl insulin (DASI). To investigate the influence of crosslinking on the dynamics of the insulin moiety, the bridge was removed from a transient DASI structure and simulation was carried on independently with the then unlinked (ULKI) as well as with the crosslinked species. The effects of crystal packing and quaternary interactions were checked by simulating both types of monomers and dimers known from the hexamer structure. All simulations were compared to previous ones of native insulin. DASI shows general similarity to the native simulations in most parts of the structure. Deviations are visible in the segments to which the bridge is directly connected, i.e. their flexibility is reduced. Upon removal of the bridge the ULKI simulations reapproach those of native insulin. The influence of the bridge spreads over the whole molecule, but all of its main structural features remain intact. The simulations suggest that the displacement of the C-terminal B chain of native insulin, considered important for receptor interaction, is prevented by the bridge, which also partially shields some binding residues. This is in accordance with the poor biological potency of A1-B29-crosslinked insulins.Abbreviations DASI-insulin(DASI)
bovineN
-A1-N
-B29-di-aminosuberoyl insulin
- ULK-insulin (ULKI)
Native beef insulin with the bridge of DASI removed 相似文献
24.
Marie Arnaud Stefan Krause Richard J. Norby Thuong Huyen Dang Nezha Acil Nicholas Kettridge Vincent Gauci Sami Ullah 《Global Change Biology》2023,29(12):3256-3270
Mangroves are among the most carbon-dense ecosystems worldwide. Most of the carbon in mangroves is found belowground, and root production might be an important control of carbon accumulation, but has been rarely quantified and understood at the global scale. Here, we determined the global mangrove root production rate and its controls using a systematic review and a recently formalised, spatially explicit mangrove typology framework based on geomorphological settings. We found that global mangrove root production averaged ~770 ± 202 g of dry biomass m−2 year−1 globally, which is much higher than previously reported and close to the root production of the most productive tropical forests. Geomorphological settings exerted marked control over root production together with air temperature and precipitation (r2 ≈ 30%, p < .001). Our review shows that individual global changes (e.g. warming, eutrophication, drought) have antagonist effects on root production, but they have rarely been studied in combination. Based on this newly established root production rate, root-derived carbon might account for most of the total carbon buried in mangroves, and 19 Tg C lost in mangroves each year (e.g. as CO2). Inclusion of root production measurements in understudied geomorphological settings (i.e. deltas), regions (Indonesia, South America and Africa) and soil depth (>40 cm), as well as the creation of a mangrove root trait database will push forward our understanding of the global mangrove carbon cycle for now and the future. Overall, this review presents a comprehensive analysis of root production in mangroves, and highlights the central role of root production in the global mangrove carbon budget. 相似文献
25.
Mutualism is thought to face a threat of coextinction cascade because the loss of a member species could lead to the extinction of the other member. Despite this common emphasis on the perils of such knock-on effect, hitherto, the evolutionary causes leading to extinction have been less emphasised. Here, we examine how extinction could be triggered in mutualism and whether an evolutionary response to partner loss could prevent collateral extinctions, by theoretically examining the coevolution of the host exploitation by symbionts and host dependence on symbiosis. Our model reveals that mutualism is more vulnerable to co-extinction through adaptive evolution (evolutionary double suicide) than parasitism. Additionally, it shows that the risk of evolutionary double suicide rarely promotes the backward evolution to an autonomous (non-symbiotic) state. Our results provide a new perspective on the evolutionary fragility of mutualism and the rarity of observed evolutionary transitions from mutualism to parasitism. 相似文献
26.
Migration is ubiquitous and can strongly shape food webs and ecosystems. Less familiar, however, is that the majority of life cycle, seasonal and diel migrations in nature are partial migrations: only a fraction of the population migrates while the other individuals remain in their resident ecosystem. Here, we demonstrate different impacts of partial migration rendering it fundamental to our understanding of the significance of migration for food web and ecosystem dynamics. First, partial migration affects the spatiotemporal distribution of individuals and the food web and ecosystem-level processes they drive differently than expected under full migration. Second, whether an individual migrates or not is regularly correlated with morphological, physiological, and/or behavioural traits that shape its food-web and ecosystem-level impacts. Third, food web and ecosystem dynamics can drive the fraction of the population migrating, enabling the potential for feedbacks between the causes and consequences of migration within and across ecosystems. These impacts, individually and in combination, can yield unintuitive effects of migration and drive the dynamics, diversity and functions of ecosystems. By presenting the first full integration of partial migration and trophic (meta-)community and (meta-)ecosystem ecology, we provide a roadmap for studying how migration affects and is affected by ecosystem dynamics in a changing world. 相似文献
27.
Yonglan Liu Mingzhen Zhang Hyunbum Jang Ruth Nussinov 《Protein science : a publication of the Protein Society》2023,32(1):e4504
Bcr-Abl, a nonreceptor tyrosine kinase, is associated with leukemias, especially chronic myeloid leukemia (CML). Deletion of Abl's N-terminal region, to which myristoyl is linked, renders the Bcr-Abl fusion oncoprotein constitutively active. The substitution of Abl's N-terminal region by Bcr enables Bcr-Abl oligomerization. Oligomerization is critical: it promotes clustering on the membrane, which is essential for potent MAPK signaling and cell proliferation. Here we decipher the Bcr-Abl specific, step-by-step oligomerization process, identify a specific packing surface, determine exactly how the process is structured and identify its key elements. Bcr's coiled coil (CC) domain at the N-terminal controls Bcr-Abl oligomerization. Crystallography validated oligomerization via Bcr-Abl dimerization between two Bcr CC domains, with tetramerization via tight packing between two binary assemblies. However, the structural principles guiding Bcr CC domain oligomerization are unknown, hindering mechanistic understanding and drugs exploiting it. Using molecular dynamics (MD) simulations, we determine that the binary complex of the Bcr CC domain serves as a basic unit in the quaternary complex providing a specific surface for dimer–dimer packing and higher-order oligomerization. We discover that the small α1-helix is the key. In the binary assembly, the helix forms interchain aromatic dimeric packing, and in the quaternary assembly, it contributes to the specific dimer–dimer packing. Our mechanism is supported by the experimental literature. It offers the key elements controlling this process which can expand the drug discovery strategy, including by Bcr CC-derived peptides, and candidate residues for small covalent drugs, toward quenching oligomerization, supplementing competitive and allosteric tyrosine kinase inhibitors. 相似文献
28.
Crosslinking mass spectrometry captures protein structures in solution. The crosslinks reveal spatial proximities as distance restraints, but do not easily reveal which of these restraints derive from the same protein conformation. This superposition can be reduced by photo-crosslinking, and adding information from protein structure models, or quantitative crosslinking reveals conformation-specific crosslinks. As a consequence, crosslinking MS has proven useful already in the context of multiple dynamic protein systems. We foresee a breakthrough in the resolution and scale of studying protein dynamics when crosslinks are used to guide deep-learning-based protein modelling. Advances in crosslinking MS, such as photoactivatable crosslinking and in-situ crosslinking, will then reveal protein conformation dynamics in the cellular context, at a pseudo-atomic resolution, and plausibly in a time-resolved manner. 相似文献
29.
Barry E. Willner Chien-Ping Lu Willard L. Miranker 《Journal of mathematical biology》1995,33(8):829-866
Hebbian dynamics is used to derive the differential equations for the synaptic strengths in the neural circuitry of the locomotive oscillator. Initially, neural connection are random. Under a specified arborization hypothesis relating to the density of neural connections, the differential equations are shown to model the self-organization and the stability of the oscillator. 相似文献
30.
Previous experience with the Langevin/implicit-Euler scheme for dynamics (“LI”) on model systems (butane, water) has shown that LI is numerically stable for timesteps in the 5–20 fs range but quenches high-frequency modes. To explore applications to polypeptides, we apply LI to model systems (several dipeptides, a tetrapeptide, and a 13-residue oligoalanine) and also develop a new dynamics driver approach (“DA”). The DA scheme, based on LI, addresses the important issue of proper sampling, which is unlikely to be solved by small-time step integration methods or implicit methods with intrinsic damping at room temperature, such as LI. Equilibrium averages, time-dependent molecular properties, and sampling trends at room temperature are reported for both LI and DA dynamics simulations, which are then compared to those generated by a standard explicit discretization of the Langevin equation with a 1 fs timestep. We find that LI's quenching effects are severe on both the fast and slow (due to vibrational coupling) frequency modes of all-atom polypeptides and lead to more restricted dynamics at moderate timesteps (40 fs). The DA approach empirically counteracts these damping effects by adding random atomic perturbations to the coordinates at each step (before the minimization of a dynamics function). By restricting the energetic fluctuations and controlling the kinetic energy, we are able with a 60 fs timestep to generate continuous trajectories that sample more of the relevant conformational space and also reproduce reasonably Boltzmann statistics. Although the timescale for transition may be accelerated by the DA approach, the transitional. information obtained for the alanine dipeptide and the tetrapeptide is consistent with that obtained by several other theoretical approaches that focus specifically on the determination of pathways. While the trajectory for oligoalanine by the explicit scheme over the nanosecond timeframe remains in the vicinity of the full αR-helix starting structure, and a high-temperature (6000°K) MD trajectory departs slowly from the a helical structure, the DA-generated trajectory for the same CPU time exhibits unfolding and refolding and reveals a range of conformations with an intermediate helix content. Significantly, this range of states is more consistent with spectroscopic experiments on small peptides, as well as the cooperative two-state model for helix–coil transition. The good, near-Boltzmann statistics reported for the smaller systems above, in combination with the interesting oligoalanine results, suggest that DA is a promising tool for efficiently exploring conformational spaces of biomolecules and exploring folding/unfolding processes of polypeptides. © 1995 Wiley-Liss, Inc. 相似文献