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111.
Estrogens are required for the proliferation of hormone dependent breast cancer cells, making estrogen receptor (ER) positive tumors amenable to endocrine therapies such as antiestrogens. However, resistance to these agents remains a significant cause of treatment failure. We previously demonstrated that inactivation of the retinoblastoma protein (pRb) family tumor suppressors causes antiestrogen resistance in MCF-7 cells, a widely studied model of estrogen responsive human breast cancers. In this study, we investigate the mechanism by which pRb inactivation leads to antiestrogen resistance. Cdk4 and cdk2 are two key cell cycle regulators that can phosphorylate and inactivate pRb, therefore we tested whether these kinases are required in cells lacking pRb function. pRb family members were inactivated in MCF-7 cells by expressing polyomavirus large tumor antigen (PyLT), and cdk activity was inhibited using the cdk inhibitors p16(INK4A) and p21(Waf1/Cip1). Cdk4 activity was no longer required in cells lacking functional pRb, while cdk2 activity was required for proliferation in both the presence and absence of pRb function. Using inducible PyLT cell lines, we further demonstrated that pRb inactivation leads to increased cyclin A expression, cdk2 activation and proliferation in antiestrogen arrested cells. These results demonstrate that antiestrogens do not inhibit cdk2 activity or proliferation of MCF-7 cells in the absence of pRb family function, and suggest that antiestrogen resistant breast cancer cells resulting from pRb pathway inactivation would be susceptible to therapies that target cdk2. 相似文献
112.
Goldman AS Guisinger VH Aikins M Amarillo ML Belizario VY Garshong B Gyapong J Kabali C Kamal HA Kanjilal S Kyelem D Lizardo J Malecela M Mubyazi G Nitièma PA Ramzy RM Streit TG Wallace A Brady MA Rheingans R Ottesen EA Haddix AC 《PLoS neglected tropical diseases》2007,1(1):e67
Background
Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk.Methodology/Principal Findings
To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1) the total annual cost of the LF program, 2) the average cost per person treated, and 3) the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1) the age (newness) of the MDA program, 2) the use of volunteers, and 3) the size of the population treated. Substantial contributions by governments were documented – generally 60%–90% of program operation costs, excluding costs of donated medications.Conclusions/Significance
MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones. 相似文献113.
As proteomic MS has increased in throughput, so has the demand to catalogue the increasing number of peptides and proteins observed by the community using this technique. As in other 'omics' fields, this brings obvious scientific benefits such as sharing of results and prevention of unnecessary repetition, but also provides technical insights, such as the ability to compare proteome coverage between different laboratories, or between different proteomic platforms. Journals are also moving towards mandating that proteomics data be submitted to public repositories upon publication. In response to these demands, several web-based repositories have been established to store protein and peptide identifications derived from MS data, and a similar number of peptide identification software pipelines have emerged to deliver identifications to these repositories. This paper reviews the latest developments in public domain peptide and protein identification databases and describes the analysis pipelines that feed them. Recent applications of the tools to pertinent biological problems are examined, and through comparing and contrasting the capabilities of each system, the issues facing research users of web-based repositories are explored. Future developments and mechanisms to enhance system functionality and user-interfacing opportunities are also suggested. 相似文献
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115.
Organisms Diversity & Evolution - Chaetopteridae — the parchment worms — comprise a group of early branching annelids with a scarcely investigated neuroanatomy and neurogenesis. Due... 相似文献
116.
Andrea Swei Kerry E. OConnor Lisa I. Couper Jose Thekkiniath Patricia A. Conrad Kerry A. Padgett Joseph Burns Melissa H. Yoshimizu Ben Gonzales Brandon Munk Nicholas Shirkey Lora Konde Choukri Ben Mamoun Robert S. Lane Anne Kjemtrup 《International journal for parasitology》2019,49(2):95-103
Babesiosis is a potentially fatal tick-borne zoonotic disease caused by a species complex of blood parasites that can infect a variety of vertebrates, particularly dogs, cattle, and humans. In the United States, human babesiosis is caused by two distinct parasites, Babesia microti and Babesia duncani. The enzootic cycle of B. microti, endemic in the northeastern and upper midwestern regions, has been well characterised. In the western United States, however, the natural reservoir host and tick vector have not been identified for B. duncani, greatly impeding efforts to understand and manage this zoonotic disease. Two and a half decades after B. duncani was first described in a human patient in Washington State, USA, we provide evidence that the enzootic tick vector is the winter tick, Dermacentor albipictus, and the reservoir host is likely the mule deer, Odocoileus hemionus. The broad, overlapping ranges of these two species covers a large portion of far-western North America, and is consistent with confirmed cases of B. duncani in the far-western United States. 相似文献
117.
Journal of Mathematical Biology - The stationary distribution of a sample taken from a Wright–Fisher diffusion with general small mutation rates is found using a coalescent approach. The... 相似文献
118.
Nicole C. Thunes Rachel A. Conrad Haitham H. Mohammed Yongtao Zhu Paul Barbier Jason P. Evenhuis David Perez-Pascual Jean-Marc Ghigo Ryan S. Lipscomb John R. Schneider Nan Li Devon H. Erbes Clayton Birkett Benjamin R. LaFrentz Timothy J. Welch Mark J. McBride 《Applied and environmental microbiology》2022,88(3)
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120.
Methane production in littoral sediment of Lake Constance 总被引:7,自引:0,他引:7
Maximum rates of CH4 production in the littoral sediment were observed in 2–5 cm depth. The CH4 production rates increased during the year from about 5 mmol m−2d−1 in December to a maximum of about 95 mmol m−2d−1 in September. CH4 production rates showed a temperature optimum at 30°C and an apparent activation energy of 76 kJ mol−1. A large part of the seasonality of CH4 production could be ascribed to the change of the sediment temperature. Most of the produced CH4 was lost by ebullition. Gas bubbles contained about 60–70% CH4 with an average δ13C of −56.2% and δD of −354%, and 2% CO2 with an average δ13C of −14.1% indicating that CH4 was produced from methyl carbon, i.e. mainly using acetate as methanogenic substrate. This result was confirmed by inhibition of methanogenesis with chloroform which resulted in an accumulation rate of acetate equivalent to 81% of the rate of CH4 production. Most probable numbers of methanogenic bacteria were in the order of 104 bacteria g−1d.w. sediment for acetate-, methanol- or formate-utilizing, and of 105 for H2-utilizing methanogens. The turnover times of acetate were in the order of 2.3–4.8 h which, with in situ acetate concentrations of about 25–50 μM, resulted in rates of acetate turnover which were comparable to the rates of CH4 production. The respiratory index (RI) showed that [2−14C]acetate was mainly used by methanogenesis rather than by respiratory processes, although the zone of CH4 production in the sediment overlapped with the zone of sulfate reduction. 相似文献