全文获取类型
收费全文 | 36517篇 |
免费 | 2772篇 |
国内免费 | 3365篇 |
出版年
2023年 | 623篇 |
2022年 | 697篇 |
2021年 | 1118篇 |
2020年 | 1118篇 |
2019年 | 1434篇 |
2018年 | 1358篇 |
2017年 | 1092篇 |
2016年 | 1015篇 |
2015年 | 1192篇 |
2014年 | 1928篇 |
2013年 | 2315篇 |
2012年 | 1571篇 |
2011年 | 2034篇 |
2010年 | 1582篇 |
2009年 | 1795篇 |
2008年 | 1929篇 |
2007年 | 1912篇 |
2006年 | 1763篇 |
2005年 | 1559篇 |
2004年 | 1448篇 |
2003年 | 1376篇 |
2002年 | 1122篇 |
2001年 | 800篇 |
2000年 | 752篇 |
1999年 | 695篇 |
1998年 | 639篇 |
1997年 | 584篇 |
1996年 | 498篇 |
1995年 | 499篇 |
1994年 | 502篇 |
1993年 | 478篇 |
1992年 | 448篇 |
1991年 | 357篇 |
1990年 | 329篇 |
1989年 | 298篇 |
1988年 | 254篇 |
1987年 | 246篇 |
1986年 | 228篇 |
1985年 | 360篇 |
1984年 | 421篇 |
1983年 | 311篇 |
1982年 | 376篇 |
1981年 | 271篇 |
1980年 | 264篇 |
1979年 | 245篇 |
1978年 | 204篇 |
1977年 | 140篇 |
1976年 | 126篇 |
1975年 | 114篇 |
1974年 | 105篇 |
排序方式: 共有10000条查询结果,搜索用时 265 毫秒
1.
《Microbes and infection / Institut Pasteur》2015,17(2):109-117
Ebola virus infection can cause Ebola virus disease (EVD). Patients usually show severe symptoms, and the fatality rate can reach up to 90%. No licensed medicine is available. In this review, development of therapeutics for treatment of Ebola virus infection and EVD will be discussed. 相似文献
2.
Pyrazolo[4,3-e][1,2,4]triazine sulfonamides as carbonic anhydrase inhibitors with antitumor activity
《Bioorganic & medicinal chemistry》2014,22(9):2643-2647
A series of sildenafil analogues and aniline substituted pyrazolo[4,3-e][1,2,4]triazine sulfonamides were prepared and evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors and for their anticancer activity against two human breast cancer cell lines (MCF-7, MDA-MB-231). The new compounds were ineffective as CA I inhibitors, poorly inhibited CA II, but were more effective against the tumor-associated isoforms CA IX and XII, with some compounds acting as low nanomolar inhibitors. Evaluation of the cytotoxicity by using an MTT assay, the inhibition of [3H]thymidine incorporation into DNA as well as collagen synthesis inhibition, demonstrated that these sulfonamides exhibit cytotoxic effects on breast cancer cell lines ex vivo. 相似文献
3.
An ATP-Sensitive K+ Current that Regulates Progression Through Early G1 Phase of the Cell Cycle in MCF-7 Human Breast Cancer Cells 总被引:4,自引:0,他引:4
Whole-cell recordings were used to identify in MCF-7 human breast cancer cells the ion current(s) required for progression
through G1 phase of the cell cycle. Macroscopic current-voltage curves were fitted by the sum of three currents, including
linear hyperpolarized, linear depolarized and outwardly rectifying currents. Both linear currents, but not the outwardly rectifying
current, were increased by 1 μm intracellular Ca2+ and blocked by 2 mm intracellular ATP. When tested at concentrations previously shown to inhibit proliferation by 50%, linogliride, glibenclamide
and quinidine inhibited the linear hyperpolarized current, and quinidine and linogliride inhibited the linear depolarized
current; none of these agents affected the outwardly rectifying current. In contrast, tetraethylammonium completely inhibited
the outwardly rectifying current, but did not inhibit either linear current. Changing the bath solution to symmetric K+ shifted the reversal potential of the linear hyperpolarized current from near the K+ equilibrium potential (−84 mV) to −4 mV. Arrest of the cell cycle in early G1 by quinidine was associated with significantly
smaller linear hyperpolarized currents, without a change in the linear depolarized or outwardly rectifying currents, but this
reduction was not observed with arrest by lovastatin at a site ≈6 hr later in G1. The linear hyperpolarized current was significantly
larger in ras-transformed than in untransformed cells. We conclude that the linear hyperpolarized current is an ATP-sensitive K+ current required for progression of MCF-7 cells through G1 phase.
Received: 22 January 1999/Revised: 11 May 1999 相似文献
4.
Patchouli virus X, a new potexvirus from Pogostemon clabin 总被引:1,自引:0,他引:1
P E MEISSNER FILHO R de O RESENDE M I LIMA E W KITAJIMA 《The Annals of applied biology》2002,141(3):267-274
This work describes a potexvirus obtained from patchouli, Pogostemon clabin, collected in São Paulo, Brazil in 1992. The plants showed mosaic and were infected by a potyvirus and a potexvirus. The potexvirus had a host range limited to Amaranthaceae, Solanaceae and Labiatae and was named Patchouli virus X (PatVX). PatVX was not transmitted by scissors pruning, in tobacco seeds or by Myzus nicotinae. The virus was purified and a specific antiserum with a titre great than 1:512 000 in dot‐ELISA was produced. The virus was serologically related to Papaya mosaic virus, Potato virus X, Viola mottle virus, White clover mosaic virus and Lily virus X. It had a coat protein of 21 071 ± 1 010 Mr. as determined by SDS‐PAGE. Immunolabelling tests demonstrated that fibrillar masses in the cytoplasm contain the coat protein. The presence of a dsRNA was detected in PatVX infected plants. 相似文献
5.
Devin M. Drown Michael J. Wade 《Evolution; international journal of organic evolution》2014,68(10):3039-3046
Populations evolve in response to the external environment, whether abiotic (e.g., climate) or biotic (e.g., other conspecifics). We investigated how adaptation to biotic, heritable environments differs from adaptation to abiotic, nonheritable environments. We found that, for the same selection coefficients, the coadaptive process between genes and heritable environments is much faster than genetic adaptation to an abiotic nonheritable environment. The increased rate of adaptation results from the positive association generated by reciprocal selection between the heritable environment and the genes responding to it. These associations result in a runaway process of adaptive coevolution, even when the genes creating the heritable environment and genes responding to the heritable environment are unlinked. Although tightening the degree of linkage accelerates the coadaptive process, the acceleration caused by a comparable amount of inbreeding is greater, because inbreeding has a cumulative effect on reducing functional recombination over generations. Our results suggest that that adaptation to local abiotic environmental variation may result in the rapid diversification of populations and subsequent reproductive isolation not directly but rather via its effects on heritable environments and the genes responding to them. 相似文献
6.
Takatoshi Murata Tsutomu Sato Takeshi Kamoda Hiromitsu Moriyama Yasuo Kumazawa Nobuhiro Hanada 《Experimental cell research》2014
Hydrogen sulfide (H2S) is a novel gasotransmitter that plays multiple biological roles in various body systems. In addition to its endogenous production, H2S is produced by bacteria colonizing digestive organs, including the oral cavity. H2S was previously shown to enhance pro-apoptotic effects in cancer cell lines, although the mechanisms involved remain unclear. To properly assess the anti-cancer effects of H2S, however, investigations of apoptotic effects in normal cells are also necessary. The aims of this study were (1) to compare the susceptibility to H2S-induced apoptosis between the oral cancer cell line Ca9-22 and oral keratinocytes that were derived from healthy gingiva, and (2) to identify candidate genes involved in the induction of apoptosis by H2S. The susceptibility to H2S-induced apoptosis in Ca9-22 cells was significantly higher than that in keratinocytes. H2S exposure in Ca9-22 cells, but not keratinocytes, enhanced the expression of pleckstrin homology-like domain, family A, member 1 (PHLDA1), which was identified through a differential display method. In addition, PHLDA1 expression increased during actinomycin D-induced apoptosis in Ca9-22 cells. Knockdown of PHLDA1 expression by small interfering RNA in Ca9-22 cells led to expression of active caspase 3, thus indicating apoptosis induction. The tongue cancer cell line SCC-25, which expresses PHLDA1 at a high level, showed similar effects. Our data indicate that H2S is an anti-cancer compound that may contribute to the low incidence of oral cancer. Furthermore, we demonstrated the role of PHLDA1 as an apoptosis suppressor. 相似文献
7.
DNA replication is a fundamental process of the cell that ensures accurate duplication of the genetic information and subsequent transfer to daughter cells. Various pertubations, originating from endogenous or exogenous sources, can interfere with proper progression and completion of the replication process, thus threatening genome integrity. Coordinated regulation of replication and the DNA damage response is therefore fundamental to counteract these challenges and ensure accurate synthesis of the genetic material under conditions of replication stress. In this review, we summarize the main sources of replication stress and the DNA damage signaling pathways that are activated in order to preserve genome integrity during DNA replication. We also discuss the association of replication stress and DNA damage in human disease and future perspectives in the field. 相似文献
8.
In a eutrophic lake, a crash of the algal population was followed by a significant increase in the number of virus-like particles (from ca. 1 106 ml–1 to ca. 26 106 ml–1), and soon thereafter by an increase of the amount of extracellular DNA (from ca. 20 µg l–1 to ca. 40 µg l–1). The same pattern of correlation between decrease of algae and increase of viruses and extracellular DNA could be demonstrated by an in vitro experiment with a Chlorella-virus-system. Lysis of algae by viruses increased both the number of viruses and the amount of DNA in the culture medium. Extracellular DNA mainly consisted of material with a molecular weight below 500 bp.The Chlorella-virus-system is discussed. It could be used as a model-system for studying the dynamics of interaction of viruses and algae in aquatic ecosystems. 相似文献
9.
The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid-state NMR spectra, conformation-dependent 15N and 13C NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide 1H nuclei, and quantitative measurements of site-specific 15N–15N dipole–dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that structures of the N-terminal domain (NTD) and the C-terminal domain (CTD) observed in solution are largely retained. However, specific segments, including the N-terminal β-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD–CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 310-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD–CTD interface, while structural variations within NTD hexamers, around local 3-fold symmetry axes, and in CTD–CTD dimerization interfaces are less significant. 相似文献
10.