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Rats with lesions of the area postrema (APX) are known to exhibit an enhanced intake of highly palatable foods such as sweetened condensed milk and cookies. These observations suggest the possibility that APX rats find these foods more rewarding and will work harder to obtain these foods. Sham and APX rats were tested on fixed ratio (FR) and progressive ratio (PR) schedules. APX rats consistently pressed more times to receive sucrose solution and attained both FR 3 and FR 5 criteria significantly faster than sham-lesioned control rats. Furthermore, rats with APX had significantly higher break points than sham-lesioned control rats on a progressive ratio schedule. These results support the hypothesis that rats with lesions of the area postrema will consistently work harder to obtain a highly palatable food reward. 相似文献
34.
R L Sandin E R Rodriguez E Rosenberg K Porter-Jordan M Caparas S Nasim M Rockis J F Keiser C T Garrett 《Journal of virological methods》1991,32(2-3):181-191
Although traditional tube culture (TTC) is still considered by many as the 'gold standard' for the laboratory diagnosis of human cytomegalovirus (HCMV), the shell vial assay (SVA) offers greater speed of detection. This technique utilizes immunofluorescence (IF) to detect early or immediate early nuclear antigens (IEA). The detection capabilities of these two tests were compared with the polymerase chain reaction (PCR), a technique that amplifies enzymatically selected DNA target sequences. Serial dilutions of crude culture harvests from 2 HCMV strains, Towne and a clinical urine isolate, were made up to 1:1 000,000. Ten-microliters aliquots of the original sample and each dilution were tested by PCR, TTC and SVA. For PCR, the nested-primer approach was used. Outer primers delimited a 721-bp sequence contained within the 2nd to 4th exons of the immediate-early protein. Inner nest primers delimited a 167-bp sequence in the third exon, detected by a 32P-labelled probe. The results show that: (1) control samples which contained all PCR reagents but no DNA were uniformly negative; (2) radiolabelled-probe detection (RPD) of PCR products is, on average, 100 x more sensitive than detection by ethidium bromide; (3) PCR is, on average, 100 x more sensitive than evaluation of cytopathic effect (CPE) in the TTC; (4) the predictive value of a negative SVA result is low compared to PCR. 相似文献
35.
Oculocutaneous albinism type II (OCA2) is the most common form of albinism in humans. OCA2 has been previously associated with mutations of the P gene, the human homologue to the murine pink-eyed dilution gene. The P gene encodes a 110 kDa protein containing 12 potential membrane spanning domains and is associated with melanosomal membranes. The specific function of the P protein is currently unknown but is thought to be involved in tyrosinase processing and transport. We report nine novel mutations in the P gene associated with OCA2. These include two missense mutations, c.1938A>C (p.Ile646Val) and c.1556T>C (p.Val519Ala); one nonsense mutation c.612G>A (p.Trp204X); five frameshift mutations: c.2372_2373delTC, c.1555delG, c.1938_1939insC, c.2050delT, and c.1045_1046delAT; and a splice site mutation c.1951+1G>A. We also report 12 novel polymorphisms including one amino acid substitution, c.2365_2366GC>CA (p.Ala789Glu). At present, there is no functional assay to determine if a mutation is truly pathogenic. The presence of numerous polymorphisms of the P gene in the coding region, several of which result in amino acid substitutions, makes molecular diagnosis problematic. To ensure accurate molecular diagnosis, further mutational analysis will be necessary to produce a comprehensive list of mutations associated with OCA2. This information will also help define the critical functional domains of the P protein. Mutations associated with OCA2 can be found in the Albinism Database (http://albinismdb.med.umn.edu). 相似文献
36.
Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia 总被引:1,自引:0,他引:1
Matthew G. Guenther Lee N. Lawton Tatiana Rozovskaia Garrett M. Frampton Stuart S. Levine Thomas L. Volkert Carlo M. Croce Tatsuya Nakamura Eli Canaani Richard A. Young 《Genes & development》2008,22(24):3403-3408
Mixed-lineage leukemia (MLL) fusion proteins are potent inducers of leukemia, but how these proteins generate aberrant gene expression programs is poorly understood. Here we show that the MLL-AF4 fusion protein occupies developmental regulatory genes important for hematopoietic stem cell identity and self-renewal in human leukemia cells. These MLL-AF4-bound regions have grossly altered chromatin structure, with histone modifications catalyzed by trithorax group proteins and DOT1 extending across large domains. Our results define direct targets of the MLL fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in cancer. 相似文献
37.
Virus persists in beta cells of islets of Langerhans and infection is associated with chemical manifestations of diabetes. II. Morphologic observations. 总被引:1,自引:1,他引:1 下载免费PDF全文
M. Rodriguez R. S. Garrett M. Raitt P. W. Lampert M. B. Oldstone 《The American journal of pathology》1985,121(3):497-504
Persistence of lymphocytic choriomeningitis (LCM) virus in the islets of Langerhans was associated with mild hyperglycemia and abnormal glucose tolerance test results. Early histopathologic events consisted of occasional perivascular inflammatory mononuclear cells around both islet and acinar cells. Morphometric studies showed an increase in the size of islets from virus-infected mice. By electron microscopy, LCM virions were found within infected beta cells. Cytolytic injury of beta cells was minimal and did not account for the abnormalities of glucose metabolism. In contrast to the findings in islets, ultrastructural studies of acinar cells revealed LCM virions in abundance, vacuolar degeneration, and intracytoplasmic inclusions. This study extends the previous observation that LCM virus infection may persist in beta cells of the islets of Langerhans without causing structural injury but be associated with abnormalities resembling the chemical and histopathologic features of the early stage of Type II (adult-onset) human diabetes mellitus. 相似文献
38.
Motor nerves of salivary myoepithelial cells in dogs 总被引:3,自引:2,他引:3
1. The pressures in the ducts of the parotid and submaxillary glands were recorded in dogs under chloralose-urethane anaesthesia. A single stimulus applied to the parasympathetic nerve regularly caused a pressure rise of short duration. Usually it did not evoke secretion.2. In both glands a single stimulus applied to the vagosympathetic trunk usually caused a pressure response of short duration. It had no secretory effect.3. In the parotid gland, repetitive vagosympathetic stimulation caused a sustained increase of pressure in the duct, usually without inducing secretion.4. In the submaxillary gland, repetitive vagosympathetic stimulation caused a sustained pressure rise, even when the secretory response had been abolished by propranolol.5. It is concluded that the salivary myoepithelial cells of dogs are supplied with fibres from both sympathetic and parasympathetic divisions of the autonomic nervous system and both can cause the cells to contract. 相似文献
39.
Investigation of synthetic Escherichia coli heat-stable enterotoxin as an immunogen for swine and cattle. 总被引:2,自引:0,他引:2 下载免费PDF全文
J C Frantz P K Bhatnagar A L Brown L K Garrett J L Hughes 《Infection and immunity》1987,55(5):1077-1084
In its native form Escherichia coli heat-stable enterotoxin (STa) is nonantigenic; however, neutralizing antibodies are elicited in animals vaccinated with toxin-carrier conjugates. To study the immunogenicity of STa, peptides STa1-18 and STa5-18 were synthesized, characterized, and conjugated to carrier proteins. Pregnant gilts and heifers were hyperimmunized with the respective conjugates. Following parturition neonates were challenged with virulent E. coli (K99+ STa+). Peptides coupled to ovalbumin and emulsified with Freund adjuvant elicited antibodies that neutralized toxin-induced fluid accumulation in suckling mice. Peptides coupled to particulate carriers, with or without muramyl dipeptide adjuvant, failed to induce a measurable response. Peak antibody levels in sera were observed following three doses of conjugate and persisted for several weeks. The serological response in cattle was superior to that observed in swine; however, antibody levels in porcine colostrum were higher than those observed in cattle. Clinical observations of neonates from vaccinated dams indicated that passively obtained antibody provided partial protection from disease, but not as complete as that demonstrable with whole cell bacterins that induce antibody to pili. However, the data suggest the potential for utility of synthetically prepared antigens. 相似文献
40.
McKernan RM Rosahl TW Reynolds DS Sur C Wafford KA Atack JR Farrar S Myers J Cook G Ferris P Garrett L Bristow L Marshall G Macaulay A Brown N Howell O Moore KW Carling RW Street LJ Castro JL Ragan CI Dawson GR Whiting PJ 《Nature neuroscience》2000,3(6):587-592
Inhibitory neurotransmission in the brain is largely mediated by GABA(A) receptors. Potentiation of GABA receptor activation through an allosteric benzodiazepine (BZ) site produces the sedative, anxiolytic, muscle relaxant, anticonvulsant and cognition-impairing effects of clinically used BZs such as diazepam. We created genetically modified mice (alpha1 H101R) with a diazepam-insensitive alpha1 subtype and a selective BZ site ligand, L-838,417, to explore GABA(A) receptor subtypes mediating specific physiological effects. These two complimentary approaches revealed that the alpha1 subtype mediated the sedative, but not the anxiolytic effects of benzodiazepines. This finding suggests ways to improve anxiolytics and to develop drugs for other neurological disorders based on their specificity for GABA(A) receptor subtypes in distinct neuronal circuits. 相似文献