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101.
D. Stein R. Maayan A. Ram R. Loewenthal A. Achiron D. Modan-Moses M. Feigin A. Weizman A. Valevski 《European neuropsychopharmacology》2005,15(6):647-653
Nineteen female adolescent inpatients diagnosed with anorexia nervosa, restricting type (AN-R) and 16 non-eating disordered (ED) controls were assessed for plasma dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulphate (DHEA-S), and cortisol levels, and for eating-related and non-eating-related psychopathology. AN-R patients were assessed at admission, 1 month and 4 months following hospitalization. The non-ED controls were assessed once. No baseline between-group differences were found in plasma cortisol, DHEA, and DHEA-S levels, whereas the patient group had a significantly lower Cortisol/DHEA-S ratio and elevated scores on most psychopathological parameters. A significant increase was found in the body mass index of the AN-R patients at 4 months post-hospitalization, accompanied by a decrease in plasma cortisol levels and a trend towards decreased Cortisol/DHEA and Cortisol/DHEA-S ratios, whereas no change occurred in psychopathology. The difference in Cortisol/DHEA-S ratio between AN-R patients and non-ED controls, and the different patterns of change in cortisol vs. DHEA(-S) levels following weight restoration, may in part account for the feeding difficulties in AN, particularly during refeeding. 相似文献
102.
DNA double-strand breaks (DSBs), the most hazardous DNA lesions, may result in genomic instability, a hallmark of cancer cells. The main DSB repair pathways are non-homologous end joining (NHEJ) and homologous recombination (HR). In mammalian cells, NHEJ, which can lead to inaccurate repair, predominates. HR repair (HRR) is considered accurate and is restricted to S, G2 and M phases of the cell cycle. Despite its importance, many aspects regarding HRR remain unknown. Here, we developed a novel inducible on/off switch cell system that enables, for the first time, to induce a DSB in a rapid and reversible manner in human cells. By limiting the duration of DSB induction, we found that non-persistent endonuclease-induced DSBs are rarely repaired by HR, whereas persistent DSBs result in the published HRR frequencies (non-significant HR frequency versus frequency of ~10%, respectively). We demonstrate that these DSBs are repaired by an accurate repair mechanism, which is distinguished from HRR (most likely, error-free NHEJ). Notably, our data reveal that HRR frequencies of endonuclease-induced DSBs in human cells are >10-fold lower than what was previously estimated by prevailing methods, which resulted in recurrent DSB formation. Our findings suggest a role for HRR mainly in repairing challenging DSBs, in contrast to uncomplicated lesions that are frequently repaired by NHEJ. Preventing HR from repairing DSBs in the complex and repetitive human genome probably has an essential role in maintaining genomic stability. 相似文献
103.
104.
Mouse models in oncogenesis and cancer therapy 总被引:3,自引:0,他引:3
María Virtudes Céspedes Isolda Casanova Matilde Parreño Ramón Mangues PhD 《Clinical & translational oncology》2006,8(5):318-329
Animal models have been critical in the study of the molecular mechanisms of cancer and in the development of new antitumor
agents; nevertheless, there is still much room for improvement. The relevance of each particular model depends on how close
it replicates the histology, physiological effects, biochemical pathways and metastatic pattern observed in the same human
tumor type. Metastases are especially important because they are the main determinants of the clinical course of the disease
and patient survival, and are the target of systemic therapy. The generation of clinically relevant models using the mouse
requires their humanization, since differences exist in transformation and oncogenesis between human and mouse. Although genetically
modified (GM) mice have been instrumental in understanding the molecular mechanisms involved in tumor initiation, they have
been less successful in replicating advanced cancer. Moreover, a particular genetic alteration frequently leads to different
tumor types in human and mouse and to lower metastastatic rates in GM mice than in humans. These findings question the capacity
of current GM mouse carcinoma models to predict clinical response to therapy. On the other hand, orthotopic (ORT) xenografts
of human tumors, or tumor cell lines, in nude mice reproduced the histology and metastatic pattern of most human tumors at
advanced stage. Usingex vivo genetic manipulation of human tumor cells, ORT models can be used to molecularly dissect the metastatic process and to evaluatein vivo tumor response to therapy, using non-invasive procedures. Nevertheless, this approach is not useful in the study of the initial
stages of tumorigenesis or the contribution of the immune system in this process. Despite ORT models are more promising than
the most commonly used subcutaneous xenografts in preclinical drug development, their capacity to predict clinical response
to antitumor agents remains to be studied. Humanizing mouse models of cancer will most likely require the combined use of
currently available methodologies.
Supported by an unrestricted educational grant from AstraZeneca. 相似文献
105.
Gallardo E. Medina J. Sánchez J. C. Viúdez A. Grande E. Porras I. Ramón y Cajal T. Trigo J. Iglesias L. Capdevila J. 《Clinical & translational oncology》2020,22(2):223-235
Clinical and Translational Oncology - Thyroid carcinoma is the most frequent endocrine malignancy and accounts for around 3% of global cancer incidence. Different histologies and clinical scenarios... 相似文献
106.
Antonio Jimeno Cristina Grávalos Pilar Escudero Isabel Sevilla M. Eugenia Vega-Villegas Vicente Alonso Ignacio Juez Rocío García-Carbonero Humberto Bovio Ramón Colomer Hernán Cortés-Funes 《Clinical & translational oncology》2008,10(1):52-57
Objective The objectives of this phase I/II study were to determine the maximum tolerated dose (MTD), characterise the principal toxicities
in the phase I part and assess the efficacy in the phase II part of gefitinib, an oral selective inhibitor of the epidermal
growth factor receptor, in combination with capecitabine in patients with advanced colorectal cancer (CRC).
Methods and patients Patients with advanced CRC were treated with gefitinib administered daily for 21 days and capecitabine administered twice
daily for 14 days of a 21-day cycle. The dose levels of gefitinib (mg) and capecitabine (mg/m2 bid) assessed were 250/1000 and 250/ 1250. An expanded cohort was enrolled at the MTD to better characterise toxicity and
efficacy. A total of 32 previously treated patients were accrued. In the phase I part 10 subjects were treated, with one dose-limiting
toxicity. Overall 26 patients were treated at the MTD of the combination, which was gefitinib 250 mg/day and capecitabine
1250 mg/m2 twice daily.
Results The most frequent treatment-related adverse events included asthenia, diarrhoea, nausea, rash and anorexia. The incidence
profile was very similar in phases I and II. No objective responses were documented but 53% of the patients achieved stable
disease as best response to therapy.
Conclusions Capecitabine 1250 mg/m2 twice daily 14 of 21 days and gefitinib at 250 mg/day can be safely administered in combination. The combination is relatively
well tolerated. There were no objective responses, although an interesting stabilisation rate was documented, in previously
treated advanced CRC patients. 相似文献
107.
Jrme Ateudjieu David A Sack Sonia Sonkeng Nafack Shaoming Xiao Ketina Hirma Tchio-Nighie Herve Tchokomeni Landry Beyala Bitaa Paul Ntsekendio Nyibio Etienne Guenou Kedia Mayah Mondung Frank Forex Kiadjieu Dieumo Rosanne Minone Ngome Kelsey N. Murt Malathi Ram Mohammad Ali Amanda K. Debes 《The American journal of tropical medicine and hygiene》2022,107(5):974
108.
Catherine E. Arnold Logan J. Voegtly Emily K. Stefanov Matthew R. Lueder Andrea E. Luquette Robin H. Miller Haven L. Miner Andrew J. Bennett Lindsay Glang Tara N. McGinnis Kristie E. Reisinger Jae W. Dugan Michael A. Mangat Daniel J. Silberger Rebecca L. Pavlicek Chaselynn M. Watters Gregory K. Rice Francisco Malagon Regina Z. Cer Stephen M. Eggan Kimberly A. Bishop-Lilly 《Viruses》2022,14(9)
The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the disparity between developed and developing countries for infectious disease surveillance and the sequencing of pathogen genomes. The majority of SARS-CoV-2 sequences published are from Europe, North America, and Asia. Between April 2020 and January 2022, 795 SARS-CoV-2-positive nares swabs from individuals in the U.S. Navy installation Camp Lemonnier, Djibouti, were collected, sequenced, and analyzed. In this study, we described the results of genomic sequencing and analysis for 589 samples, the first published viral sequences for Djibouti, including 196 cases of vaccine breakthrough infections. This study contributes to the knowledge base of circulating SARS-CoV-2 lineages in the under-sampled country of Djibouti, where only 716 total genome sequences are available at time of publication. Our analysis resulted in the detection of circulating variants of concern, mutations of interest in lineages in which those mutations are not common, and emerging spike mutations. 相似文献
109.
Noam Barda Michal Canetti Mayan Gilboa Victoria Indenboim Keren Asraf Yael Weiss-Ottolenghi Sharon Amit Daniel Zibly Ram Doolman Ella Mendelson Dror Harats Laurence S. Freedman Yitshak Kreiss Yaniv Lustig Gili Regev-Yochay 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(39)
We assess the immunogenicity and efficacy of Spikevax and Comirnaty as fourth dose COVID-19 vaccines. Six months post-fourth-dose, IgG levels were higher than pre-fourth dose at 1.58-fold (95% CI: 1.27–1.97) in Spikevax and 1.16-fold (95% CI: 0.98–1.37) in Comirnaty vaccinees. Nearly 60% (159/274) of vaccinees contracted SARS-CoV-2. Infection hazard ratios (HRs) for Spikevax (0.82; 95% CI: 0.62–1.09) and Comirnaty (0.86; 95% CI: 0.65–1.13) vaccinees were similar, as were substantial-disease HRs, i.e. 0.28 (95% CI: 0.13–0.62) and 0.51 (95% CI: 0.27–0.96), respectively. 相似文献
110.
Deepa Shrestha Sahajal Dhooria Ganesh Kumar Munirathinam Inderpaul Singh Sehgal Kuruswamy Thurai Prasad Babu Ram Harkant Singh Ashutosh N. Aggarwal Goverdhan D Puri Valliappan Muthu Ritesh Agarwal 《Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders》2022,39(2)